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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... 1,62 Diabetes was considered to be rare in the first half of the twentieth century in the USA; less than 1% of the population was diagnosed with diabetes in 1958. 63,64 However, both the incidence and prevalence of T2D increased throughout the second half of the 20th century in developed countries, becoming an epidemic towards the end of the century and remaining as such into the 21st century. 1,63 Over recent decades, T2D incidence and prevalence have also increased in developing countries, becoming a comparable health burden in these countries. ...
... 63,64 However, both the incidence and prevalence of T2D increased throughout the second half of the 20th century in developed countries, becoming an epidemic towards the end of the century and remaining as such into the 21st century. 1,63 Over recent decades, T2D incidence and prevalence have also increased in developing countries, becoming a comparable health burden in these countries. In 1980, <1% of China's population had diabetes but this increased to almost 10% by 2008. ...
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Type 2 diabetes (T2D), which has currently become a global pandemic, is a metabolic disease largely characterised by impaired insulin secretion and action. Significant progress has been made in understanding T2D aetiology and pathogenesis, which is discussed in this review. Extrapancreatic pathology is also summarised, which demonstrates the highly multifactorial nature of T2D. Glucagon-like peptide (GLP)-1 is an incretin hormone responsible for augmenting insulin secretion from pancreatic beta-cells during the postprandial period. Given that native GLP-1 has a very short half-life, GLP-1 mimetics with a much longer half-life have been developed, which are currently an effective treatment option for T2D by enhancing insulin secretion in patients. Interestingly, there is continual emerging evidence that these therapies alleviate some of the post-diagnosis complications of T2D. Additionally, these therapies have been shown to induce weight loss in patients, suggesting they could be an alternative to bariatric surgery, a procedure associated with numerous complications. Current GLP-1-based therapies all act as orthosteric agonists for the GLP-1 receptor (GLP-1R). Interestingly, it has emerged that GLP-1R also has allosteric binding sites and agonists have been developed for these sites to test their therapeutic potential. Recent studies have also demonstrated the potential of bi-and tri-agonists, which target multiple hormonal receptors including GLP-1R, to more effectively treat T2D. Improved understanding of T2D aetiology/ pathogenesis, coupled with the further elucidation of both GLP-1 activity/targets and GLP-1R mechanisms of activation via different agonists, will likely provide better insight into the therapeutic potential of GLP-1-based therapies to treat T2D.
... The prevalence of diabetes mellitus (DM) and DM-related complications has been convincingly described regarding clinical, social, and economic implications (American Diabetes Association, 2018;Sørensen et al., 2016). By 2030, there will be approximately 430 million people with DM worldwide (Ginter and Simko, 2012). The incidence rate of diabetic foot ulcers (DFUs) in this cohort is increasing to around 20%, with an average annual cost of $8,659 for one patient in the United States (American Diabetes Association, 2018; Ginter and Simko, 2012). ...
... By 2030, there will be approximately 430 million people with DM worldwide (Ginter and Simko, 2012). The incidence rate of diabetic foot ulcers (DFUs) in this cohort is increasing to around 20%, with an average annual cost of $8,659 for one patient in the United States (American Diabetes Association, 2018; Ginter and Simko, 2012). Diabetic patients with foot ulcers are at a high risk of operative limb salvage programs, including even major and minor amputations (Wukich et al., 2017). ...
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Lack of vascularization is directly associated with refractory wound healing in diabetes mellitus (DM). Enrichment of endothelial precursor cells (EPCs) is a promising but challenging approach for the treatment of diabetic wounds. Herein, we investigate the action of nicotinamide riboside (NR) on EPC function for improved healing of diabetic wounds. Db/db mice that were treated with NR-supplemented food (400 mg/kg/d) for 12 weeks exhibited higher wound healing rates and angiogenesis than untreated db/db mice. In agreement with this phenotype, NR supplementation significantly increased the number of blood EPCs and bone marrow (BM)-derived EPCs of db/db mice, as well as the tube formation and adhesion functions of BM-EPCs. Furthermore, NR-supplemented BM-EPCs showed higher expression of sirtuin 1 (Sirt1), phosphorylated adenosine monophosphate–activated protein kinase (p-AMPK), and lower expression of acetylated peroxisome proliferator–activated receptor γ coactivator (PGC-1α) than BM-EPCs isolated from untreated db/db mice. Knockdown of Sirt1 in BM-EPCs significantly abolished the tube formation and adhesion function of NR as well as the expression of p-AMPK and deacetylated PGC-1a. Inhibition of AMPK abolished the NR-regulated EPC function but had no effect on Sirt1 expression, demonstrating that NR enhances EPC function through the Sirt1-AMPK pathway. Overall, this study demonstrates that the oral uptake of NR enhances the EPC function to promote diabetic wound healing, indicating that NR supplementation might be a promising strategy to prevent the progression of diabetic complications.
... Diabetes mellitus (DM) is an increasing global and regional public health challenge [1][2][3][4]. It's estimated that there was about 381.8 million adults with DM worldwide in 2013 and the number is expected to increase to 55% by 2035 [2]. ...
... 3) ...
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Diabetes mellitus (DM) is an increasing health challenge. Control of blood glucose level, as measured by level of glycated hemoglobin (HbA1c), is used as an indicator of glycemic control and potential risk of diabetic complications. This study aimed to investigate the extent of glycemic control among type 2 diabetic patients and to determine factors associated with increasing levels of HbA1c.A total of 380 patients were interviewed using a questionnaire prepared for this cross-sectional study. The patients were recruited from a diabetic clinic in Nablus, Palestine. Clinical laboratory data and HbA1c values were obtained from medical files of the patients while demographic information were obtained through face-to-face interview. The participants had a mean ± standard deviation (SD) age of 60 ± 10 years. A total of 71 (18.7%) participants were less than 50 years of age. The participants had a mean body mass index (BMI) of 32.7± 6 Kg/m 2 with more than two thirds were considered obese with a BMI of ≥ 30 Kg/m 2. The studied patients have a mean ± SD of HbA1c of 8.3± 1.8. The median of HbA1c was 8.05 with interquartile range of (First quartile (Q1) = 6.93; Third quartile (Q3) = 9.5). The majority of studied patients (278; 73.2%) had HbA1c value above 7%. The mean ± SD healthcare index (HCI) of the studied patients was 4.29 ± 1.49. Univariate analysis showed that age (p<0.01), total cholesterol (p<0.01), low density lipoprotein (LDL) (p<0.01), high density lipoprotein (HDL) (p=0.028), HIC (p<0.01), and type of therapeutic regimen (p<0.01) were significantly correlated with HbA1c. Multivariate analysis indicated that younger age, lower HDL values, combination therapy with insulin were significantly associated with increasing levels of HbA1c.High proportion of patients recruited for this study had poor glycemic control. Younger age was associated with higher HbA1c values which necessitates urgent and immediate medical intervention at the primary healthcare level.
... The rising prevalence of several chronic diseases (1)(2)(3)(4)(5) [e.g., obesity, type 2 diabetes (T2D), and hypertension] worldwide has been described as global puzzles and public health problems (6)(7)(8). The relationship between exercise and health promotion has been gradually explored and studied. ...
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Background: High-intensity interval training (HIIT) is an emerging exercise strategy and is considered to be a recipe for health promotion. This study aimed to systematically identify collaboration networks, track research trends, highlight current hotspots, and predict future frontiers in HIIT and its applications in health promotion since the start of the new century. Methods: Relevant original publications were obtained from the Science Citation Index Expanded of the Web of Science Core Collection (WoSCC) database between 2001 and 2020. CiteSpace and VOSviewer software were used to perform bibliometric visualization and comparative analysis of involved indexes that included countries, institutions, journals, authors, references, and keywords. Results: A total of 572 papers were included, and the trend of annual publications showed a remarkable growth. The United States and the University of Exeter were the most productive country and institutions, respectively, with 107 and 18 publications, respectively. European Journal of Applied Physiology took the lead in the number of published articles, and Medicine and Science in Sports and Exercise ranked first in the cocitation counts. Barker AR and Gibala MJ were considered as the most productive and the most highly-cited authors. Conclusions: “Health risks,” “adolescent,” and “aging” are the three noteworthy topics during the evolution of HIIT-health promotion (HIIT-HP) research. The current research hotspots of HIIT and its practices in the health promotion domain lies in “metabolic diseases,” “cardiovascular diseases,” “neurological diseases,” and “musculoskeletal diseases.” The authors summarize that “prevention and rehabilitation,” “micro and molecular level,” and “cognition and mental health” are becoming frontiers and focus on the health topics related to HIIT in the upcoming years, which are worthy of further exploration.
... Type 2 diabetes is the most common metabolic disease, and it is one of the leading causes for blindness, cardiovascular disease and end-stage kidney disease. 1,2 Insulin resistance at target tissues and an impaired insulin secretion in pancreatic beta cells are central to the development of type 2 diabetes. [3][4][5] Increasing evidence suggests that mitochondria play a role in both processes and mitochondrial dysfunction has therefore been implicated to have a key role in the development of type 2 diabetes. ...
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Background: Type 2 diabetes is associated with both impaired insulin action at target tissues and impaired insulin secretion in pancreatic beta-cells. Mitochondrial dysfunction may play a role in both insulin resistance and impaired insulin secretion. Plasma creatine has been proposed as a potential marker for mitochondrial dysfunction. We aimed to investigate the association between plasma creatine and incident type 2 diabetes. Methods: We measured fasting plasma creatine concentrations by nuclear magnetic resonance spectroscopy in participants of the general population-based PREVEND study. The study outcome was incident type 2 diabetes, defined as a fasting plasma glucose ≥7.0 mmol/l (126 mg/dl); a random sample plasma glucose ≥11.1 mmol/l (200 mg/dl); self-report of a physician diagnosis or the use of glucose lowering medications based on a central pharmacy registration. Associations of plasma creatine with type 2 diabetes were quantified using Cox proportional hazards models and were adjusted for potential confounders. Results: We included 4,735 participants aged 52 ± 11 years, of whom 49% were male. Mean plasma creatine concentrations were 36.7 ± 17.6 µmol/L, with lower concentrations in males than in females (30.4 ± 15.1 µmol/L versus 42.7 ± 17.7 µmol/L; P for difference <0.001). During 7.3 [6.2 - 7.7] years of follow-up, 235 (5.4%) participants developed incident type 2 diabetes. Higher plasma creatine concentrations were associated with an increased risk of incident type 2 diabetes (HR per SD change: 1.27 [95% CI: 1.11 - 1.44]; P<0.001), independent of potential confounders. This association was strongly modified by sex (P interaction <0.001). Higher plasma creatine was associated with an increased risk of incident type 2 diabetes in males (HR: 1.40 [1.17 - 1.67]; P<0.001), but not in females (HR: 1.10 [0.90 - 1.34]; P=0.37). Conclusion: Fasting plasma creatine concentrations are lower in males than in females. Higher plasma creatine is associated with an increased risk of type 2 diabetes in males.
... Due to vitamin D deficiency and the risk of related diseases, in many countries there is a legal obligation to enrich certain products (dairy products, especially milk and other dairy drinks, margarines) or vitamin D3 enriched products for infants and children, because the content of Vitamin D3 in breast milk is relatively low [2]. ...
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Background Vitamin D has a widely acknowledged role in regulating the metabolism of calcium and phosphate, both essential to bone remodeling. However, numerous studies in recent decades have emphasized the association between low sun exposure and vitamin D deficiency, and an increased risk of extra-skeletal disorders such as cancer. Objective This mini-review of literature aims to present an objective overview of several recent studies and meta-analyses evaluating the role of vitamin D in cancer prevention, its potential to improve cancer treatment outcomes, as well as the negative effects of vitamin D deficiencies. Methods The antitumor effects of calcitriol and analogs in the treatment of cancer, either as single agents or in combination with other anticancer agents, are based on several mechanisms: inhibition of cancer cell proliferation and invasiveness, induction of differentiation and apoptosis, and promotion of angiogenesis, all recorded in a number of preclinical studies of several cancer types Results The importance of VDR polymorphisms for individual malignancies remains a topic of debate. Contradictory effects have been recorded in recent studies, the results of which include positive associations of VDR when cumulated with other risk factors, both an increase and a decrease in cancer risks, as well as no correlation between VDR polymorphisms and individual malignancies.. Conclusion The scientific evidence reviewed in this paper suggests that health care providers and individuals should consider increasing concentrations of 25 (OH) D through sensitive sun exposure and / or by supplementing with vitamin D to reduce cancer risk and, in combination with standard care, to treat cancer.
... [5][6][7][8][9][10][11] Type 2 diabetes mellitus (T2DM), a chronic condition in which the amount of glucose level in the human body increases, leads to these dysfunctions. [12][13][14][15][16] Unsuitable glucagon secretion, resistance to insulin action and inadequate insulin secretion can lead to T2DM. [17][18][19][20][21] Nonpharmacological interventions 22,23 like diet and exercise can be quite useful in managing T2DM but in most of the cases, eventually the patient has to rely on pharmacological drugs. ...
... 1 In our modern age, the rapidly elevated prevalence of metabolic diseases is considered as a major health problem. 2 It has been reported that more than a third of adults in the United States are diagnosed with metabolic abnormalities, most likely due to an unhealthy lifestyle. 3 As preferred alternatives to therapeutics or surgical treatments, lifestyle changes such as dietary modifications and adopting a physically more active lifestyle can be beneficial to people with metabolic dysregulations. ...
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As an alternative to pharmacological treatment to diseases, lifestyle interventions, such as dietary changes and physical activities, can help maintain healthy metabolic conditions. Recently, the emerging analyses of volatile organic compounds (VOCs) from breath and short-chain fatty acids (SCFAs) from plasma/feces have been considered as useful tools for the diagnosis and mechanistic understanding of metabolic diseases. Furthermore, diet-induced changes of SCFAs in individuals with diagnosed metabolic abnormalities have been correlated with the composition changes of the gut microbiome. More interestingly, the analysis of exhaled breath (breathomics) has gained attention as a useful technique to measure the human VOC profile altered as a result of dietary interventions. In this mini-review, we examined recent clinical trials that performed promising dietary interventions, SCFAs analysis in plasma/feces, and VOC profile analysis in exhaling breath to understand the relationship between dietary intervention and metabolic health.
... Obesity and its common pathological outcome type 2 diabetes have emerged as primary risk factors for the increased morbidity and mortality in recent decades (Ginter & Simko, 2012;Nichols, Joshua-Gotlib, & Parasuraman, 2013). The cellular cAMP and cGMP signaling and its A. Samidurai, L. Xi, A. Das et al. ...
Article
Cyclic nucleotide phosphodiesterases (PDEs) are superfamily of enzymes that regulate the spatial and temporal relationship of second messenger signaling in the cellular system. Among the 11 different families of PDEs, phosphodiesterase 1 (PDE1) sub-family of enzymes hydrolyze both 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP) in a mutually competitive manner. The catalytic activity of PDE1 is stimulated by their binding to Ca2+/calmodulin (CaM), resulting in the integration of Ca2+ and cyclic nucleotide-mediated signaling in various diseases. The PDE1 family includes three subtypes, PDE1A, PDE1B and PDE1C, which differ for their relative affinities for cAMP and cGMP. These isoforms are differentially expressed throughout the body, including the cardiovascular, central nervous system and other organs. Thus, PDE1 enzymes play a critical role in the pathophysiology of diseases through the fundamental regulation of cAMP and cGMP signaling. This comprehensive review provides the current research on PDE1 and its potential utility as a therapeutic target in diseases including the cardiovascular, pulmonary, metabolic, neurocognitive, renal, cancers and possibly others.
... T2DM is characterized by impaired insulin secretion and tolerance, hyperinsulinemia, and hyperglycemia, and describes a group of clinical syndromes resulting from glucose metabolism disorders triggered by genetic or environmental factors. It has become a global public health concern with a wide range of complications, such as hypertension, coronary heart disease, renal failure, and stroke (42). Genetic factors are at the center of T2DM disease development and pathogenesis (43,44), and 40 susceptibility loci have been described to date (45). ...
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Context Type 2 diabetes mellitus (T2DM) and cancer share a variety of risk factors and pathophysiological features. It is becoming increasingly accepted that the two diseases are related, and that T2DM increases the risk of certain malignancies. This review summarizes recent advancements in the elucidation of functions of insulin-like growth factor 2 (IGF-2) mRNA-binding protein 2 (IGF2BP2) in T2DM and cancer. Evidence Acquisition A PubMed review of the literature was conducted, and search terms included: IGF2BP2, IMP2, or p62 in combination with cancer or T2DM. Additional sources were identified through manual searches of reference lists. Evidence Synthesis The increased risk of multiple malignancies and cancer-associated mortality in patients with T2DM is believed to be driven by insulin resistance, hyperinsulinemia, hyperglycemia, chronic inflammation, and dysregulation of adipokines and sex hormones. Furthermore, IGF-2 is oncogenic, and its loss-of-function splice variant is protective against T2DM, which highlights the pivotal role of this growth factor in the pathogenesis of these two diseases. IGF-2 mRNA-binding proteins, particularly IGF2BP2, are also involved in T2DM and cancer, and single nucleotide polymorphisms of IGF2BP2 are associated with both diseases. Deletion of the IGF2BP2 gene in mice improves their glucose tolerance and insulin sensitivity and mice with transgenic p62, a splice variant of IGF2BP2, are prone to diet-induced fatty liver disease and hepatocellular carcinoma, suggesting the biological significance of IGF2BP2 in T2DM and cancer. Conclusions Accumulating evidence revealed that IGF2BP2 mediates the pathogenesis of T2DM and cancer by regulating glucose metabolism, insulin sensitivity, and tumorigenesis. This review provides insight into the potential involvement of this RNA binding protein in the link between T2DM and cancer.
... The first and second derivatives of the spectra (D1 and D2) based on the Savitzky-Golay algorithm, with five smoothing points and polynomial order of 2, were also implemented to increase the spectral resolution. Derivatives are commonly used to reduce insignificant baseline signals from samples [25]. ...
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Background and aim: The literature is scant on the effect of 11-keto-β-boswellic acid (KBA) on the liver of diabetes-induced mice. This study was designed to develop a rapid, sensitive, accurate, and inexpensive detection technique for evaluating the solubility of KBA obtained from the gum resin of Omani frankincense (Boswellia sacra) in the liver of streptozotocin-induced diabetic mice using Fourier transform infrared (FTIR) reflectance spectroscopy coupled with principal components analysis (PCA). It also aimed to investigate the effect of KBA on histological changes in the hepatocytes of diabetic mice. Materials and methods: Eighteen mice were assigned to the healthy control group, the diabetic control group, or the KBA-treated diabetic group. Liver tissue samples from all groups were scanned using an FTIR reflectance spectrophotometer in reflection mode. FTIR reflectance spectra were collected in the wavenumber range of 400-4000 cm-1 using an attenuated total reflectance apparatus. Results: FTIR reflectance spectra were analyzed using PCA. The PCA score plot, which is an exploratory multivariate data set, revealed complete segregation among the three groups' liver samples based on changes in the variation of wavenumber position in the FTIR reflectance spectra, which indicated a clear effect of KBA solubility on treatments. Histological analysis showed an improvement in the liver tissues, with normal structures of hepatocytes exhibiting mild vacuolation in their cytoplasm. Conclusion: KBA improved the morphology of liver tissues in the diabetic mice and led to complete recovery of the damage observed in the diabetic control group. FTIR reflectance spectroscopy coupled with PCA could be deployed as a rapid, low-cost, and non-destructive detection method for evaluating treatment effects in diseased liver tissue based on the solubility of KBA.
... Type 2 diabetes (T2D) is one of the major risk factors for developing cardiovascular (CV) disease and the resultant devastating morbidity and mortality in the world [1,2]. The main features of T2D are hyperglycemia, hyperlipidemia, insulin resistance and reduced insulin production in the late stages of the disease. ...
Article
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Type 2 diabetes (T2D) is one of the major risk factors for developing cardiovascular disease and the resultant devastating morbidity and mortality. The key features of T2D are hyperglycemia, hyperlipidemia, insulin resistance, and impaired insulin secretion. Patients with diabetes and myocardial infarction have worse prognosis than those without T2D. Moreover, obesity and T2D are recognized risk factors in developing severe form of COVID-19 with higher mortality rate. The current lines of drug therapy are insufficient to control T2D and its serious cardiovascular complications. Phosphodiesterase 5 (PDE5) is a cGMP specific enzyme, which is the target of erectile dysfunction drugs including sildenafil, vardenafil, and tadalafil. Cardioprotective effects of PDE5 inhibitors against ischemia/reperfusion (I/R) injury were reported in normal and diabetic animals. Hydroxychloroquine (HCQ) is a widely used antimalarial and anti-inflammatory drug and its hyperglycemia-controlling effect in diabetic patients is also under investigation. This review provides our perspective of a potential use of combination therapy of PDE5 inhibitor with HCQ to reduce cardiovascular risk factors and myocardial I/R injury in T2D. We previously observed that diabetic mice treated with tadalafil and HCQ had significantly reduced fasting blood glucose and lipid levels, increased plasma insulin and insulin-like growth factor-1 levels, and improved insulin sensitivity, along with smaller myocardial infarct size following I/R. The combination treatment activated Akt/mTOR cellular survival pathway, which was likely responsible for the salutary effects. Therefore, pretreatment with PDE5 inhibitor and HCQ may be a potentially useful therapy not only for controlling T2D but also reducing the rate and severity of COVID-19 infection in the vulnerable population of diabetics.
... World Health Organization (WHO) defines type 2 DM as increased sugar levels on two instances: First one considers fasting plasma glucose (FPG) greater than 7.0 mmol/L. Secondly by using a glucose tolerance test (GTT), in which plasma glucose level of 11.1 mmol/L was considered as a threshold after 2 h of oral glucose administration (Ginter and Simko 2013). ...
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Type 2 diabetes mellitus is a complicated metabolic disorder with no definite treatment. Cyperus iria (Cyperaceae) possess several traditional therapeutic uses. According to the folklore tales, the whole plant of Cyperus iria possesses antihyperglycemic activity. The present study was undertaken to investigate whether aqueous-ethanol extract of Cyperus iria can ameliorate the altered activities of carbohydrate metabolism in streptozotocin (STZ)-induced diabetic rats along with appraisal of inflammatory and stress markers involved in endocrine dysfunction. Presence of biophenolics and flavonoids might be responsible for the antidiabetic potential. STZ-induced diabetic rats were treated orally with Cyperus iria extract (125, 250, and 500 mg/kg) for 15 days. Blood samples were collected. Metformin was used as positive control. Significantly higher quantities of phenolic (82.79±0.003 mg/g GAE) and flavonoid (13.61±0.002 mg/g QE) contents were present. Inhibitory concentration (IC50) exhibited an excellent potential for both antioxidant (IC50= 3.22 μg/mL) and alpha amylase (IC50=36.29 μg/mL) inhibitory assays. High-performance liquid chromatography (HPLC) confirmed the existence of myercetin, quercetin, kaempferol, and ferulic acid. Cyperus iria aqueous-ethanol extract exhibits good tolerance against glucose at 90 min in normal rats. Streptozotocin-induced hyperglycemia declined significantly at day 9 (265 mg/dL) along with improvement in inflammatory (TNF-α=15.6± 0.2 g/l, COX-2=357±0.396 U/l, IL-6= 572±0.99 pg/l) and oxidative stress markers (SOD= 163±0.616 and GSH-ST= 95.8±0.44 U/mL) along with biochemical parameters in a dose-dependent manner. Present study suggests that Cyperus iria aqueous-ethanol extract possesses hypoglycemic potential which might be attributed to the decrease in oxidative stress and inflammatory markers.
... (Defronzo RA et al., 2015 ). The major symptoms include increased thirst, frequent urination, weight loss, and fatigue (Ginter E et al., 2013). ...
... Although there has been controversy over whether insulin resistance or β-cell defect is a priority, recent epidemiological studies have emphasized that insulin resistance is a primary abnormality in T2DM. [3][4][5] It has been pointed out that activated inflammatory response has an important role in the pathogenesis of T2DM. Additionally, β-cell death and chronic hyperglycemia can be triggered by pro-inflammatory cytokines and chemokines. ...
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Inflammation is the natural immunological response of an organism against any harmful, foreign or destructive effect to heal and repair damaged tissue. The nod-like receptor pyrin domain-containing-3 (NLRP3) inflammasome is one of the main components of the inflammatory mechanism and is associated with many inflammatory diseases, but it is also closely related to metabolic abnormalities, such as type 2 diabetes mellitus (T2DM), insulin resistance and obesity. NLRP3 activates inflammation and causes interleukin-1β release, exogenous and endogenous danger signals, as well as insulin resistance. In this direction, we focus on the gene structure of NLRP3 in diabetes and accordingly, we aim to determine the relationship between eight gene variations in the NLRP3 gene and T2DM. We investigated the rs10802501, rs10733113, rs10754558, rs10925026, rs10925027, rs35829419, rs4612666 and rs4925659 single-nucleotide polymorphisms of NLRP3 gene using the Sequenom MassARRAY system in 100 T2DM patients and 100 control individuals. There were no significant differences between T2DM risk and the genotype frequencies of rs10802501, rs10733113, rs35829419 and rs10925026 variants (p > 0.05). However, significant genotype frequencies were determined for rs10925027 (p = 0.0013) and rs4925659 (p < 0.001). For the risk allele G of the rs10754558 variant, significant differences were found in the heterozygous and dominant model (p = 0.036, p = 0.033). The genotype distribution of the rs4612666 variant was significant only in the heterozygous model (p = 0.047). In this hospital-based case-control study, rs10925027, rs4925659 and rs10754558 variants were found to be closely related to T2DM risk. The rs10925027 CC genotype, rs4925659 GG genotype, rs10754558 GG and GC+GG genotypes of the NLRP3 were determined as important risk factors for the T2DM.
... Diabetes mellitus is a metabolic disease characterized by insufficient secretion or low action of pancreatic insulin with high incidence and prevalence worldwide [1]. There is an increasing trend of type 2 diabetes even in groups of the population that have low socioeconomic status [2] associated with late-diagnosed type 2 diabetes as well as uncontrolled levels of glycated hemoglobin HbA1c and cholesterol in the blood more typical in people with low educational level [3]. ...
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Type 2 diabetes is an endocrine disease with a rising incidence and prevalence worldwide in particular in low-middle income countries including Albania. Regular medication treatment, healthy lifestyle and nutrition including self-management are essential for the quality of life of patients with type 2 diabetes as well as the reduction of associated social and health costs. The purpose of the cross-sectional web survey was to evaluate the level of disease self-management in adult patients with type 2 diabetes selected using the random and snowballing methods. Data was collected in the period June-July 2020 through a standard anonymous questionnaire distributed through Google Forms. 132 patients of the age group 18-85 years were the final study sample. Mean age 42.7 years old, SD±15, 5. Women were 69 % of participants and 31% men. Statistically significant relationships were found between nutrition, physical activity, glucose monitoring, and gender, p=0.001. The results of the study showed inconsistencies in knowledge about disease self-management among the study population. Females showed better knowledge of self-management in relation to nutrition and physical activity. While men paid closer attention to the proper monitoring and management of blood glucose levels. The design and promotion of gender-based diabetes self-management educational programs are recommended.
... Type 2 diabetes mellitus (T2DM) is a progressive disease of hyperglycemia characterized by insulin resistance and beta cell dysfunction, which accounts for approximately 85-95% of all diabetes cases. 1,2 In recent years, the number of adults with diabetes in China is among the highest in the world, and its incidence is still rising sharply. 3 The treatment of T2DM imposes enormous social, financial and health system burdens in China. ...
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Purpose: This study aimed to explore the relationship between KCNQ1 polymorphism and type 2 diabetes mellitus (T2DM) risk in the population of Northwest China. Patients and methods: Case-control strategy was used to reveal the correlation between KCNQ1 polymorphism and T2DM risk, and MDR analysis clarified the influence of KCNQ1 polymorphism interaction on T2DM risk. The related proteins, functions, and signal pathways of KCNQ1 were further explored through bioinformatics methods. PCR was used to explore the relative expression of KCNQ1 in T2DM patients and the controls. Results: Studies showed that rs163177, rs163184, rs2237895 and rs2283228 on the KCNQ1 gene are closely related to the risk of T2DM in Northwest China. MDR results showed that the three-locus model is the best model for T2DM risk assessment, which increases the risk of T2DM. The bioinformatics results showed that KCNQ1 closely-acted proteins are mainly involved in signal pathways such as gastric acid secretion and renin secretion. The PCR results showed that, compared with the controls, the expression of KCNQ1 was up-regulated in T2DM patients. Conclusion: The results revealed that KCNQ1 polymorphism is related to the risk of T2DM in the population of Northwest China and provide a scientific basis for the early screening and prevention of T2DM high-risk populations.
... Insulin is a hormone produced by pancreatic β cells that increases glucose uptake by the cells, thereby reducing blood glucose levels [60]. The lack of tissue sensitivity to insulin, that is, insulin resistance, as well as defective secretion of this hormone is associated with type 2 diabetes mellitus (T2DM), defined now as a pandemic of the 21st century [60][61][62][63]. Nevertheless, its action is not limited to peripheral tissues. ...
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The ketogenic diet (KD) is a high-fat, low-carbohydrate and adequate-protein diet that has gained popularity in recent years in the context of neurological diseases (NDs). The complexity of the pathogenesis of these diseases means that effective forms of treatment are still lacking. Conventional therapy is often associated with increasing tolerance and/or drug resistance. Consequently, more effective therapeutic strategies are being sought to increase the effectiveness of available forms of therapy and improve the quality of life of patients. For the moment, it seems that KD can provide therapeutic benefits in patients with neurological problems by effectively controlling the balance between pro- and antioxidant processes and pro-excitatory and inhibitory neurotransmitters, and modulating inflammation or changing the composition of the gut microbiome. In this review we evaluated the potential therapeutic efficacy of KD in epilepsy, depression, migraine, Alzheimer’s disease and Parkinson’s disease. In our opinion, KD should be considered as an adjuvant therapeutic option for some neurological diseases.
... Type 2 diabetes (T2D) is a highly prevalent multifactorial disease caused by a combination of genetic and lifestyle factors which represents a huge societal problem associated with a significant economic burden for all healthcare systems [1,2]. T2D is characterized by high levels of plasma glucose caused mainly by pancreatic β-cell dysfunction and inefficient action of insulin, known as insulin resistance (IR), which occurs in cells of insulin-sensitive key organs and tissues such as the heart or skeletal muscle [1,3]. ...
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Background: We report that myocardial insulin resistance (mIR) occurs in around 60% of patients with type 2 diabetes (T2D) and was associated with higher cardiovascular risk in comparison with patients with insulin-sensitive myocardium (mIS). These two phenotypes (mIR vs. mIS) can only be assessed using time-consuming and expensive methods. The aim of the present study is to search a simple and reliable surrogate to identify both phenotypes. Methods: Forty-seven patients with T2D underwent myocardial [18F]FDG PET/CT at baseline and after a hyperinsulinemic-euglycemic clamp (HEC) to determine mIR were prospectively recruited. Biochemical assessments were performed before and after the HEC. Baseline hepatic steatosis index and index of hepatic fibrosis (FIB-4) were calculated. Furthermore, liver stiffness measurement was performed using transient elastography. Results: The best model to predict the presence of mIR was the combination of transaminases, protein levels, FIB-4 score and HOMA (AUC = 0.95; sensibility: 0.81; specificity: 0.95). We observed significantly higher levels of fibrosis in patients with mIR than in those with mIS (p = 0.034). In addition, we found that patients with mIR presented a reduced glucose uptake by the liver in comparison with patients with mIS. Conclusions: The combination of HOMA, protein, transaminases and FIB-4 is a simple and reliable tool for identifying mIR in patients with T2D. This information will be useful to improve the stratification of cardiovascular risk in T2D.
... Negli ultimi 20 anni, in più circostanze è stato utilizzato il termine pandemia per sottolineare che il diabete stava dilagando in tutto il mondo [1,2]. Il diabete tipo 2, in particolare, è stato indicato dalla Organizzazione Mondiale della Sanità come la malattia non trasmissibile che, insieme a due malattie trasmissibili (malaria e tubercolosi), era diventata un'emergenza planetaria [3] per una numerosità di casi che aumentava in maniera esponenziale [4] e per costi che stavano diventando elevatissimi [5]. ...
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Sommario In Italia vivono circa 4 milioni di persone con il diabete e ogni anno ci sono circa 350 mila nuove diagnosi. Le persone con diabete ricevono prescrizioni di farmaci, esami di laboratorio e strumentali e richiedono ricoveri ospedalieri più spesso delle persone senza il diabete. Il diabete è gravato da aumentata mortalità e accorcia la vita, soprattutto nelle persone di media età. La qualità della cura nelle persone con diabete è subottimale, soprattutto fra chi non è assistito nei centri diabetologici (che, peraltro, rappresentano dei luoghi “salvavita”). Il diabete contribuisce fortemente alla spesa sanitaria e comporta ingenti spese, non tutte specificamente sanitarie. Nonostante tutto questo e nonostante leggi nazionali e regionali, documenti di indirizzo nazionali e regionali, PDTA regionali e locali, promesse e proponimenti di varia provenienza, la pandemia diabete non riceve le attenzioni che merita.
... Diabetes mellitus (DM) is a form of metabolic illness with long-term elevated blood glucose levels. In every part of the globe, diabetes is growing quickly and is regarded one of the main public health hazards in the twenty-first century [1]. The prevalence of DM is expected to affect 366 million people worldwide by 2030, with 90% of cases being the disease's Type 2 DM. ...
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The present research aim is to develop the tablet formulation containing microspheres and encapsulating microsphere with antidiabetic drug specially Sitagliptin Phosphate Monohydrate and poly lactic co glycolic acid (PLGA) as a polymer. Preformulation study of the selected drug was carried out. Then, the microspheres were prepared by factorial design, i.e., Design-Expert 12 software (Stat-Ease Inc., USA) was used for designing of experiment, to study interaction between independent variables and dependent variables and deriving optimum formulation. Spray dryer was used for preparation of microspheres. The zeta potential, particle size, infrared spectral analysis, scanning electron microscopy, % drug content, encapsulation efficiency and % drug release were evaluated. Optimized batch F3 showed an average particle size 2500.6 nm. The in vitro drug release at 12th hour and % drug entrapment efficiency of optimized batch F3 was found to be 92.35% and the 34.00%, respectively. The final product has lowered particle size 2500.6 nm and it is focused for well acceptable and suitable due to significant drug release. The final tablet was prepared from optimized batch F3. The precompression parameters, i.e., flow properties of granules, were carried out, and then, post-compression parameters like weight variation, thickness, hardness, friability, % drug content and % drug release were evaluated. The stability study and in vitro antidiabetic study was carried out for tablet. The final product is well acceptable, suitable, palatable, easy for administration and elegant. Graphical abstract
... Type 2 DM is an ongoing pandemic and is among the critical diseases. 13 Many risk factors are associated with diabetes, including age, obesity, lack of physical activity, family history of diabetes, fat-rich diet, and high blood pressure. Every three years, screening is recommended for individuals over 45 years and younger people having risk factors or whose body mass index is 25 kg/m 2 . ...
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Background: Type 2 Diabetes Mellitus (DM) is another pandemic of 21 century, and its control is of immense importance. Researchers developed many predictor models using soft computing techniques. The present study developed a prediction model for Type 2 DM using machine learning classifiers. The analysis excludes plasma glucose concentration and insulin concentration as predictors to explore relationships with other predictors. Background: Methods: This cross-sectional study enrolled 108 participants aged 25 to 67 years from SMS Medical College, Jaipur (Rajasthan, India), after approval from the ethics committee. The study developed a prediction model using machine learning techniques. The classifiers used in the application include decision trees, support vector machines, K-nearest neighbors, and ensemble learning classifiers. A total of 25 predictors were collected and underwent feature reduction. The response levels include diabetes mellitus, prediabetes, and no diabetes mellitus. The models were run using three predictors and a response variable. The prediction model with the best accuracy and area under the receiver operator characteristic curve was selected. Results: The features that vary among the three groups include age, WHR, biceps skinfold thickness, total lipids, phospholipids, triglycerides, total cholesterol, LDL, VLDL, and serum creatinine, and family history of DM. After feature reduction, the age, biceps skinfold thickness, and serum creatinine were run on the Classification learner application to predict the diabetic category. The best model was subspace discriminant with accuracy, sensitivity, specificity, and AUC under the ROC curve was 62.4%, 74%, 94%, and 0.70, respectively. Conclusion: The present study concludes that age, biceps skinfold thickness, and serum creatinine combination have higher specificity in predicting type 2 DM. The study emphasized the selection of appropriate predictors along with newer machine learning algorithms.
... Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder caused by dysfunction of beta cells, which causes insulin resistance. It is one of the diseases with the highest prevalence in the 21 st century [1]. In 2011, approximately 366 million cases of diabetes mellitus were registered globally; there is an expected increase to 552 million in 2030 [2]. ...
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Background The formation of advanced glycation end products (AGEs) takes place during normal aging; however, their production is faster in people having diabetes. The accumulated AGEs reportedly play a role in the occurrence of various age-related disorders. Furthermore, the skin autofluorescence (SAF) technique can be used to detect accumulated AGEs levels. There are few reports on the association between skin accumulation of AGEs and risk of complications in type 2 diabetes mellitus. Methods In this study, we aimed to describe the association between the skin accumulation of AGEs and cardiovascular risk factors in Korean patients with type 2 diabetes. A total of 310 Korean patients with diabetes were enrolled, and the levels of AGEs were measured using SAP. Levels of fasting blood glucose (FBS), triglycerides, total cholesterol, low- and high-density lipoprotein cholesterol, proteinuria, arterial pulse wave velocity (PWV), and blood vessel age were measured using an automatic waveform analyzer. General linear models were used to identify the independent effect of AGEs after adjusting for covariates (age, weight, and duration of diabetes). Results The skin levels of AGEs were strongly correlated with the diabetes duration. Significant independent associations were observed for AGEs with FBS (P <0.01), proteinuria (P <0.001), and PWV (P <0.001). The advanced glycated product was independently associated to the arterial pulse wave conduction velocity that is used as a representative method for measuring arteriosclerosis by analysis early cardiovascular risk factors. Conclusion Our results show that an increase in SAF levels in Korean patients with type 2 diabetes is associated with PWV and vein age, and thereby with arterial stiffness. Therefore, our results suggest that AGEs are associated with cardiovascular risk factors. The level of AGEs can thus be used as an indicator of cardiovascular diseases in the clinical diagnosis of patients with type 2 diabetes.
... Hyperglycemia, in turn, is caused by defective insulin secretion or impairment of its biological activity, or both. 1 The long-term presence of hyperglycemia leads to chronic damage and dysfunction of various tissues. 1 Among different types of DM, type 2 diabetes (T2DM) accounts for the majority of cases, and the number of people with T2MD is expected to reach 366 million by 2030. 2 It is known that β cells in the pancreas are critical in maintaining glucose homeostasis during the progression to T2DM, generating compensatory hyperinsulinemia to counteract insulin resistance. 3 In vitro studies found that gastrin increases β-cell mass by inducing β-cell neogenesis and regeneration, and treatment with gastrin was found to induce the formation of new β cells in animal models. ...
Article
Background: Proton pump inhibitor use was reported to potentially provide benefits to prevent diabetes mellitus. This study aims to investigate the association between proton pump inhibitor use and the risk of developing diabetes mellitus. Methods: This study was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42021238481). A systematic literature search was conducted to identify eligible studies up to February 2021. Quality assessment was conducted according to Jadad Scoring Scale and Newcastle-Ottawa Scale. The heterogeneity among studies was tested and estimated by Q test and I2. Pooled hazard ratio with 95% CI was calculated using the random-effects or fixed-effects model depending on the heterogeneity. Subgroup analyses, sensitivity analysis, and publication bias assessment were also performed. Results: Eight studies including 850 019 participants were included. We found that proton pump inhibitor use was associated with a statistically non-significant increased risk of diabetes mellitus (pooled hazard ratio was 1.06, 95% CI = 0.89-1.28, P = .50). In subgroup analysis, 5 studies conducted in North America confirmed the overall result; however, one study conducted in Europe demonstrated a statistically significant increased risk, while one study in Asia revealed a statistically significant decreased risk. Conclusion: Proton pump inhibitor use is not associated with either increased or decreased risk of diabetes mellitus. However, more well- designed studies focusing on proton pump inhibitor use and the risk of diabetes mellitus, especially among populations with different backgrounds, are still needed.
... Desse modo, o diabetes mellitus ocasiona complicações agudas, como a hipoglicemiagrave para o cérebro, pois este é um órgão glicodependente -, bem como alterações crônicas, tal como lesões nos vasos sanguíneos, danos a estruturas oculares, diminuição da filtração renal, redução da sensibilidade periféricas e comprometimento da circulação sanguínea devido à obstrução ou estreitamento do lúmen vascular 12,13 . Com base nisso, são notórias as anormalidades a nível cerebral aliado às modificações corporais a médio e em longo prazo nas síndromes metabólicas associadas ao diabetes. ...
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Introdução: O diabetes mellitus (DM) é uma patologia metabólica relacionada à hiperglicemia, desencadeada por múltiplos fatores e possui diferentes categorias. Pacientes diabéticos têm maior probabilidade de comprometimento cognitivo e risco de Doença de Alzheimer (DA). Objetivo: Analisar a existência de evidências da correlação entre a Doença de Alzheimer e o Diabetes Mellitus. Método: Trata-se de uma revisão integrativa da literatura, realizada nas bases de dados Medical Literature Analysis and Retrieval System Online, Literatura Latino-Americana e do Caribe de Informação em Ciências da Saúde e na biblioteca da Scientific Electronic Library Online. Ademais, efetuou-se uma análise crítica dos estudos, excluindo aqueles que não respondiam à pergunta selecionada pelos autores e os textos duplicados. Resultado: A partir da seleção de 15 artigos, notou-se que aproximadamente (100%) dos estudos apontam correlações entre DM e DA, dentre os quais as principais relações foram em relação à fisiopatologia comum (33,3%), influência da dieta, microbiota, inflamação (26,6%) e sinalizações hormonais (20%) como fatores contribuintes para o desenvolvimento desses distúrbios. Conclusão: A DM e DA compartilham mecanismos de desenvolvimento semelhantes. Todavia, ainda são necessárias maiores evidências de estudos para que sejam estabelecidas estratégias resolutivas para essas patologias.
... Diabetes mellitus (DM) is a chronic disease characterized by high blood glucose levels (hyperglycemia) caused by impaired insulin secretion and insulin resistance or both [1]. The prevalence of Diabetes Mellitus globally is increasing from year to year, from 108 million people in 1980 to 422 million people in 2014. ...
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Diabetes Mellitus is a chronic disease that requires a long treatment therapy so that it requires a large amount of money. This study aims to determine the use of antidiabetics and the total cost of therapy for type 2 DM patients in Riau Province, Indonesia.This type of research is observational, descriptive. To determine direct medical costs, data were taken retrospectively from the medical records of outpatient type 2 diabetes mellitus patients at Arifin Achmad Hospital between October 2016 and March 2017.Data were also taken concurrently, namely by conducting interviews to determine direct non-medical costs in patients with type 2 diabetes mellitus. The results obtained were the average total cost per month was Rp. 375,974.54. Direct medical costs include antidiabetic costs of Rp 46,430.53, complication costs of Rp 47,246.90, doctor's examination fees of Rp 25,000, laboratory examination fees of Rp 61,183.84, and diet costs of Rp 46,798.22. Direct non-medical costs include transportation costs of Rp. 24,845.36, while indirect costs are Rp. 122,954.54.
... 13 Increasing aging population, rapid urbanization, overweight and obesity, sedentary lifestyle, and excessive intake of alcohol and unhealthy diets were identified as significant predictors to the escalation of DM worldwide. 9,14 The prevalence of DM in Africa is forecasted to triple in the coming 25 years involving young populations too, because of increasing sedentary lifestyle, fast-growing urbanization, and a shift from local traditional to processed foods. 9,15 Ethiopia is the fourth highest contributor of cases with DM in Africa in 2019, with 1.7 million total cases; 4.3% ageadjusted comparative prevalence; and 23,157 total deaths among 20-79 years old population. ...
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Background: In the past decade, the prevalence of diabetes has grown more rapidly in low- and middle-income countries than in high-income countries. In 2019, Ethiopia is the fourth highest contributor to cases with diabetes in Africa with 1.7 million total cases. The present study was aimed to determine the prevalence of abnormal glucose metabolism and associated factors in Mekelle city, Northern Ethiopia. Methods and materials: Community-based cross-sectional study was conducted among 321 randomly selected participants aged 20 years and above. Sociodemographic, lifestyle, clinical, and anthropometric data were collected in accordance with the STEPwise approach as recommended by the World Health Organization (WHO) for non-communicable disease (NCDs) surveillance. Blood glucose and lipid profiles were determined using a fasting venous blood sample. Bivariate and multivariable logistic regression analysis was used to identify factors associated with abnormal glucose metabolism. The level of statistical significance was set at p ≤0.05. Results: More than half (54.8%) of the participants were women with an overall mean (±SD) age of 39.0 (±14.2) years. The overall prevalence of pre-diabetes and diabetes was 12.5% and 9.3%, respectively, with a mean (±SD) fasting blood glucose of 97.42 (±38.03) mg/dL. More than two-thirds (70.0%) of adults with diabetes were not aware of being diabetes. Advanced age, hypercholesterolemia, medium and high rank of heart rate, and raised waist to height ratio were significantly associated with a higher risk of pre-diabetes, whereas having house servant, systolic hypertension, and hypercholesterolemia were significantly associated with diabetes. Conclusion: We found a high prevalence of prediabetes and diabetes with more than two-thirds (70.0%) of newly diagnosed adults with diabetes, which showed a lack of awareness in the community. Awareness creation together with access to basic diagnostics in the primary health-care settings should therefore be a top priority to prevent its progression and complication.
... Diabetes is considered one of the XXI century health emergencies (Ginter & Simko, 2012), affecting 465 million people worldwide (International Diabetes Federation [IDF], 2017). Ninety percent of the global diabetic population have Type 2 Diabetes Mellitus (T2DM), which may cause serious complications, negatively affecting patients' quality of life and increasing healthcare costs (IDF, 2017). ...
Article
Type 2 Diabetes Mellitus can cause serious complications; it has a severe impact on the quality of life and high costs. One of the key strategies to manage diabetes is self-care, a complex multifactorial process influenced by personal, cultural, and systemic factors, that comprises self-care maintenance, self-care monitoring, and self-care management. Few patients perform adequate self-care. To deepen our understanding of patients’ experiences of self-care maintenance, self-care monitoring, and self-care management, we conducted the first qualitative study on this topic. This study used Interpretive Phenomenological Analysis, informed by the Middle-range Theory of Self-care of Chronic Illness, to explore the experience and meaning of self-care maintenance, self-care monitoring, and self-care management in adults with T2DM (n = 10). Three themes were identified: self-care is renouncement, self-care is routine, and self-care is control. A cross-cutting moral pattern connects the three themes. Our findings corroborate the Middle-range Theory of Self-care of Chronic Illness in the field of diabetes self-care and could inform practitioners in understanding the experience of self-care as a complex phenomenon and in developing tailored interventions.
... Type 2 Diabetes Mellitus (T2DM) is a major worldwide public health problem that currently affects over 425 million people globally, and by 2045 is expected to reach 628 million. By 2030 T2DM is projected to be the 7 th most common cause of death in the world (1,2). In the Middle East and North Africa region alone, 9.6% of adults are living with T2DM, with approximately 49% undiagnosed. ...
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Aim Type 2 Diabetes Mellitus (T2DM) is associated with microvascular complications, including diabetic retinopathy (DR), diabetic nephropathy (DNp), and diabetic peripheral neuropathy (DPN). In this study, we investigated genetic variations and Single Nucleotide Polymorphisms (SNPs) associated with DR, DNp, DPN and their combinations among T2DM patients of Arab origin from the United Arab Emirates, to establish the role of genes in the progression of microvascular diabetes complications. Methods A total of 158 Emirati patients with T2DM were recruited in this study. The study population was divided into 8 groups based on the presence of single, dual, or all three complications. SNPs were selected for association analyses through a search of publicly available databases, specifically genome-wide association study (GWAS) catalog, infinome genome interpretation platform, and GWAS Central database. A multivariate logistic regression analysis and association test were performed to evaluate the association between 83 SNPs and DR, DNp, DPN, and their combinations. Results Eighty-three SNPs were identified as being associated with T2DM and 18 SNPs had significant associations to one or more diabetes complications. The most strongly significant association for DR was rs3024997 SNP in the VEGFA gene. The top-ranked SNP for DPN was rs4496877 in the NOS3 gene. A trend towards association was detected at rs833068 and rs3024998 in the VEGFA gene with DR and rs743507 and rs1808593 in the NOS3 gene with DNp. For dual complications, the rs833061, rs833068 and rs3024997 in the VEGFA gene and the rs4149263 SNP in the ABCA1 gene were also with borderline association with DR/DNp and DPN/DNp, respectively. Diabetic with all of the complications was significantly associated with rs2230806 in the ABCA1 gene. In addition, the highly associated SNPs rs3024997 of the VEGFA gene and rs4496877 of the NOS3 gene were linked to DR and DPN after adjusting for the effects of other associated markers, respectively. Conclusions The present study reports associations of different genetic polymorphisms with microvascular complications and their combinations in Emirati T2DM patients, reporting new associations, and corroborating previous findings. Of interest is that some SNPs/genes were only present if multiple comorbidities were present and not associated with any single complication.
... Saudi Med J 2021; Vol. 42(1) ...
Article
Objectives: To explore the sociodemographic and clinical characteristics as the process and outcomes of diabetic individuals. Methods: Hospital Saudi Registry at Prince Sultan Military Medical City, Chronic Illness Clinics (Family and Community Medicine), Riyadh, Saudi Arabia database was started in February 2019 and data were collected until February 2020. The data were collected by trained diabetes nurse specialists. The registry includes all patients with type II diabetes mellitus (DM) and excluded patients with type I DM. Results: A total of 8,209 patients were enrolled in the registry with a higher proportion of females than males. The mean age was 59.3 years, BMI 32.5kg/m2, and HBA1c levels was 8.2%. Significant gender differences for BMI, duration of diabetes, blood pressure, LDL, smoking status, and medication intake. From the first to the third visit, BMI was raised; however, LDL, diastolic blood pressure, and albumin creatinine ratio were reduced. The mean HBA1c values plummeted for all patients and 33% of the patients had a reduction in the HbA1c levels. However, HbA1c levels increased for 24.7% of the patients' from baseline to the last visit. Conclusion: This registry provides great insights into the sociodemographic and clinical characteristics of diabetic patients in Saudi Arabia. This registry data can be used to investigate the associations between sociodemographic or clinical characteristics and glycemic control among T2DM patients in Saudi Arabia.
Article
Scope The differences between the baseline gut microbiota of patients who developed type 2 diabetes (T2D) consuming a low‐fat (LF) or a Mediterranean (Med) diet are explored and risk scores are developed to predict the individual risk of developing T2D associated with the consumption of LF or Med diet. Methods and Results All the patients from the CORDIOPREV study without T2D at baseline (n = 462) whose fecal sample are available, are included. Gut microbiota is analyzed by 16S sequencing and the risk of T2D after a median follow‐up of 60 months assessed by Cox analysis. Linear discriminant analysis effect size (LEfSe) analysis shows a different baseline gut microbiota in patients who developed T2D consuming LF and Med diets. A higher abundance of Paraprevotella, and lower Gammaproteobacteria and B. uniformis are associated with T2D risk when an LF diet is consumed. In contrast, higher abundances of Saccharibacteria, Betaproteobacteria, and Prevotella are associated with T2D risk when a Med diet is consumed. Conclusion The results suggest that different interactions between the microbiome and dietary patterns may partially determine the risk of T2D development, which may be used for selecting personalized dietary models to prevent T2D.
Article
Background Enzymatic hydrolysis of fish protein using protease or fish protein hydrolysate can form bioactive peptides that has antidiabetes activity. One potential mechanism of fish protein hydrolysate in reducing blood glucose is through increased endogenous glucagon like peptide (GLP)-1 production. Tempeh is soy fermented food that has protease which is potential as biocatalyst in producing fish protein hydrolysate. Objective To evaluate the antidiabetic properties of Selar (Selar crumenophthalmus) fish protein hydrolysate using tempeh protease as biocatalyst and duodenal gene expression of GLP-1. Methods Selar fish protein isolate was digested for 8 hours at 37° C using crude tempeh protease. Diabetes mellitus was induced in rats by intraperitoneal injection of streptozotosin (65 mg/kg bw) and nicotinamide (230 mg/kg bw). Fish protein isolate and hydrolysate in dose of 300 mg/ bw and 500 mg/ bw were orally administered daily for 4 weeks. Blood was drawn for fasting serum glucose and lipid profile analysis. Total RNA were isolated from duodenum and quantitative real time PCR was performed to quantify mRNA expression of GLP-1. Data were analyzed using one way ANOVA and gene expression analysis were performed using Livak. Results and Discussion There is a significant difference on fasting serum glucose, total cholesterol, triglyceride, LDLcholesterol, HDL-cholesterol and duodenal GLP-1 mRNA expression level between groups (p<0.05). The duodenal GLP1 mRNA expression was the highest in rats received hydrolyzed fish protein 500 mg/ bw.
Article
Background The management of diabetes costs in excess of $1.3 trillion per annum worldwide. Diet is central to the management of type 2 diabetes. It is not known whether dietetic intervention is cost effective. This scoping review aimed to map the existing literature concerning the cost effectiveness of medical nutrition therapy provided by dietitians for people with type 2 diabetes. Methods Thirteen scientific databases, including MEDLINE, EMBASE and CINAHL, as well as multiple official websites, were searched to source peer‐reviewed articles, reports, guidelines, dissertations and other grey literature published from 2008 to present. Eligible articles had to have assessed and reported the cost effectiveness of dietetic intervention for adults with type 2 diabetes in developed countries. Experimental, quasi‐experimental, observational and qualitative studies were considered. Results Of 2387 abstracts assessed for eligibility, four studies combining 22 765 adults with type 2 diabetes were included. Dietetic intervention was shown to be cost‐effective in terms of diabetes‐related healthcare costs and hospital charges, at the same time as also reducing the risk of cumulative days at work lost to less than half and the risk of disability ‘sick’ days at work to less than one‐seventh. Conclusions The findings highlight the importance of advocacy for medical nutrition therapy for people with type 2 diabetes, with respect to alleviating the great global economic burden from this condition. Further studies are warranted to elucidate the factors that mediate and moderate cost effectiveness and to allow for the generalisation of the findings.
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MicroRNAs (miRNAs) regulate the expression of genes associated with the development of diseases, including type 2 diabetes mellitus (T2DM). However, the use of miRNAs to predict T2DM remission has been poorly studied. Therefore, we aimed to investigate whether circulating miRNAs could be used to predict the probability of T2DM remission in patients with coronary heart disease. We included the newly diagnosed T2DM (n = 190) of the 1,002 patients from the CORDIOPREV study. Seventy-three patients reverted from T2DM after 5 years of dietary intervention with a low-fat or Mediterranean diet. Plasma levels of 56 miRNAs were measured by OpenArray. Generalized linear model, receiver operating characteristic (ROC), Cox regression, and pathway analyses were performed. ROC analysis based on clinical variables showed an area under the curve (AUC) of 0.66. After a linear regression analysis, seven miRNAs were identified as the most important variables in the group’s differentiation. The addition of these miRNAs to clinical variables showed an AUC of 0.79. Cox regression analysis using a T2DM remission score including miRNAs showed that high-score patients have a higher probability of T2DM remission (hazard ratio [HR]low versus high, 4.44). Finally, 26 genes involved in 10 pathways were related to the miRNAs. We have identified miRNAs (hsa-let-7b, hsa-miR-101, hsa-miR-130b-3p, hsa-miR-27a, hsa-miR-30a-5p, hsa-miR-375, and hsa-miR-486) that contribute to the prediction of T2DM remission in patients with coronary heart disease.
Article
Background High blood pressure is common and comorbid with type 2 diabetes (T2D). Almost 50% of patients with T2D have high blood pressure. Patients with both conditions of hypertension and T2D are at risk for cardiovascular diseases and mortality. The study aim was to investigate genetic risk factors for hypertension in T2D patients. Methods This study included 999 T2D (cohort 1) patients for the first genome scan stage and 922 T2D (cohort 2) patients for the replication stage. Here, we investigated the genetic susceptibility and cumulative weighted genetic risk score for hypertension in T2D patients of Han Chinese descent in Taiwan. Results Thirty novel genetic single nucleotide polymorphisms (SNPs) were associated with hypertension in T2D after adjusting for age and body mass index (p-value < 1 x10 -4). Eight blood pressure-related and/or hypertension-related genetic SNPs were associated with hypertension in T2D after adjusting for age and body mass index (p-value < 0.05). Linkage disequilibrium (LD) and cumulative weighted genetic risk score analyzes showed that 14 of the 38 SNPs were associated with risk of hypertension in a dose-dependent manner in T2D (Cochran-Armitage trend test: p-value < 0.0001). The 14-SNPs cumulative weighted genetic risk score was also associated with increased regression tendency of systolic blood pressure in T2D (SBP = 122.05 + 0.8 x weighted GRS; p-value = 0.0001). Conclusions A cumulative weighted genetic risk score composed of 14 SNPs is important for hypertension, increased tendency of systolic blood pressure, and may contribute to hypertension risk in T2D in Taiwan.
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Background The main inhibitor of the fibrinolytic system, Plasminogen Activator Inhibitor -1 (PAI-1), irreversibly binds tissue-type Plasminogen Activator (t-PA) and thereby inhibits the protective action of tPA against thrombus formation. Elevated levels of plasma PAI-1 are associated with an increased risk of cardiovascular events and are observed in subjects with type 2 diabetes (T2D) and obesity. Platelets contain the majority of PAI-1 present in blood and exhibit the ability to synthesis active PAI-1. Diabetic platelets are known to be hyper-reactive and larger in size; however, whether these features affect their contribution to the elevated levels of plasma PAI-1 in T2D is not established. Objectives To characterize the PAI-1 antigen content and the mRNA expression in platelets from T2D subjects compared to obese and lean control subjects, in order to elucidate the role of platelet PAI-1 in T2D. Methods Nine subjects with T2D and obesity were recruited from Primary Care Centers together with 15 healthy control subjects (8 lean subjects and 7 with obesity). PAI-1 antigen levels in plasma, serum and platelets were determined by ELISA, and PAI-1 mRNA expression was analyzed by qPCR. Results There was no significant difference in PAI-1 mRNA expression or PAI-1 antigen in platelets in T2D subject in comparison to obese and lean control subjects. An elevated level of plasma PAI-1 was seen in both T2D and obese subjects. PAI-1 gene expression was significantly higher in both obese groups compared to lean. Conclusion Similar levels of protein and mRNA expression of PAI-1 in platelets from T2D, obese and lean subjects indicate a limited role of platelets for the elevated plasma PAI-1 levels. However, an increased synthesis rate of mRNA transcripts in platelets from T2D and an increased release of PAI-1 could also result in similar mRNA and protein levels. Hence, synthesis and release rates of PAI-1 from platelets in T2D and obesity need to be investigated to further elucidate the role of platelets in obesity and T2D.
Article
Context Patients with type 2 diabetes mellitus (T2DM) experience a two‐fold increased risk for cardiovascular diseases. Genome‐wide association studies (GWAS) have identified T2DM susceptibility genetic variants. Interestingly, these genetic variants associated with cardiovascular disease risk in T2DM Han Chinese remains to be elucidated. Objective To investigate the genetic variants associated with cardiovascular disease risk in T2DM. Design, Setting, and Participants We performed a boostrapping, GWAS, and investigated genetic variants associated with cardiovascular disease risk in a discovery T2DM cohort and in a replication cohort. The discovery cohort included 326 cardiovascular disease patients and 1,209 non‐cardiovascular disease patients. The replication cohort included 68 cardiovascular disease patients and 317 non‐‐cardiovascular disease patients. Main Outcome Measures Genetic variants for genetic risk score (GRS) in cardiovascular disease risk in T2DM. Results 35 genetic variants were associated with cardiovascular disease risk. A GRS was generated by combining risk alleles from these variants weighted by their estimated effect sizes (log OR). T2DM patients with weighted GRS > 12.63 had an approximately 15‐fold increase in cardiovascular disease risk (odds ratio: 15.67, 95% CI: 10.33‐24.00) compared to patients with weighted GRS < 10.39. With the addition of weighted GRS, receiver‐operating characteristic (ROC) curves showed that area under the curve (AUC) with conventional risk factors was improved from 0.719 (95% CI: 0.689‐0.750) to 0.888 (95% CI: 0.866‐0.910). Conclusions These 35 genetic variants are associated with cardiovascular disease risk in T2DM, alone and cumulatively. T2DM patients with higher levels of weighted genetic risk score have higher cardiovascular disease risks.
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Thesis
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The prevalence of metabolic disorders such as overweight, obesity and type 2 diabetes (T2D) has rapidly increased worldwide during the last decades, and physical activity has preventive as well as therapeutic benefits for these conditions. Increasing evidence suggests that dysregulations in lipid influx, storage and/or triacylglycerol (TAG) lipolysis have significant impact on insulin sensitivity and glucose homeostasis in skeletal muscle. Furthermore, it has been suggested that the insulin resistance in subjects that are overweight/obese and/or have T2D is associated with lipid accumulation in their skeletal muscles. Much of the studies that have been performed have been aimed towards the possibility of increasing lipid utilization by exercise or pharmacological activation to avoid ectopic lipid accumulation in skeletal muscle. The nuclear receptor peroxisome proliferator-activated receptor delta (PPARD) has been shown to be an important regulator of skeletal muscle lipid metabolism. This thesis aimed to study regulation of energy metabolism in cultured human skeletal muscle cells isolated from biopsies from subjects with different metabolic profile and training status, and we also studied effects of an in vivo exercise intervention on in vitro energy metabolism in the cells. Plasma lactate concentrations increase rapidly during exercise, and was initially thought of as a waste product; however, recently lactate was found to be a useable energy source in skeletal muscle. Therefore, we aimed to study lactate metabolism in cultured human myotubes at rest and to see if acute and chronic lactate exposure affected metabolism of glucose and oleic acid (OA). The lipid droplet (LD)-associated protein perilipin 2 (PLIN2) is one of several PPARD target genes, and to study the functional role of PLIN2 and LDs on energy metabolism in skeletal muscle we also examined myotubes established from Plin2+/+ and Plin2-/- mice. The 12-week training intervention, consisting of combined endurance and strength training, improved endurance, strength and insulin sensitivity in vivo, and reduced the participants’ body weight. Biopsy-derived cultured myotubes from these participants before and after the exercise intervention showed exercise-induced increase in total cellular OA uptake, oxidation and lipid accumulation, as well as increased fractional glucose oxidation (glucose oxidation relative to glucose uptake). Most of these exercise-induced increases were significant in the overweight group, whereas no changes in OA or glucose metabolism were observed in myotubes from the normal weight subjects. On the other hand, when studying energy metabolism in individuals with different inherent training status we observed higher carbohydrate and fat oxidation in vivo in trained and intermediary trained subjects compared to sedentary untrained subjects. Fiber type distribution did not differ between groups. In myotubes established from the trained compared to untrained subjects we observed higher fractional glucose oxidation, and those myotubes were also more sensitive towards the suppressive action of acutely added OA to the cells. Furthermore, myotubes from trained subjects had lower fatty acid (FA) accumulation, lower incorporation of OA into total lipids, TAG, diacylglycerol and cholesteryl ester, higher TAG-related lipolysis and re-esterification, and also higher FA complete oxidation (CO2) and β-oxidation compared to myotubes from untrained subjects. When studying lactate metabolism in myotubes established from lean healthy donors we observed that the cells expressed both of the monocarboxylate transporters, MCT1 and MCT4, and we observed that lactic acid was a usable substrate for both glycogen synthesis and incorporation into lipids. Acute addition of lactic acid inhibited glucose and OA oxidation, whereas OA uptake increased. Pretreatment with lactic acid for 24 h did not affect glucose or OA metabolism; however, when increasing the exposure time by replacing glucose with lactic acid in the cell culture media during the whole proliferation and differentiation period, glucose uptake and oxidation as well as OA oxidation were increased. Ablation of Plin2 resulted in myotubes with reduced number of LDs, reduced accumulation of TAG and higher lipolysis. Furthermore, ablation of Plin2 resulted in a metabolic shift in energy metabolism from utilization of glucose towards FAs. Despite increased oxidative capacity for FAs, the exercise intervention in vivo, high training status and ablation of Plin2 did not have any impact on insulin-stimulated responses. The results presented in this thesis shows that exercise is able to induce changes in human myotubes in vivo that are discernible in vitro and that cultured myotubes retain some the phenotypic traits of their donors. Ablation of Plin2 shifted the cells from glucose to lipid metabolism. Furthermore, the results suggest that prolonged exposure to lactate affect metabolism of glucose and FAs. Also, for the first time we show that lactic acid is a usable substrate for glycogen synthesis and it can be stored as intracellular lipids in myotubes. Thus, lactate may be an important regulator of energy metabolism in human myotubes.
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p class="abstract"> Background: Diabetes mellitus prevalence has been on the increase especially the type 2. This study therefore is to determine the pattern, type and severity of hearing impairment and correlating it with the duration, presence of peripheral neuropathy, glycaemic control of the type 2 diabetes mellitus seen in university of Port Harcourt teaching hospital (UPTH). Methods: It is a descriptive cross sectional study of adult diabetic patients seen at the endocrinology clinic of University of Port Harcourt teaching hospital. Consecutive patients with confirmed diagnosis of diabetes mellitus that gave their informed consent were recruited. A semi structured questionnaire aimed at obtaining the biodata, duration of diabetes and level of control, presence of neuropathy was administered to these patients. They had otoscopy done in addition to audiometric evaluation using pure tone audiometry. Results: The study involved 108 subjects with confirmed diagnosis of type 2 diabetes mellitus. Males; 42 and females; 66. Age ranged from 20 -81years. Hearing impairment was present in 68.52% of the subjects. Audiometric pattern showed 54.6% with SNHL while 31.5% had normal hearing. Majority of the subjects had mild degree hearing loss (50%). Bilateral SNHL was the commonly seen type of hearing loss in 55.93%. Conclusions: There is a high prevalence of hearing loss in patients with type 2 diabetes mellitus. The commonest type of hearing loss in these subjects was bilateral mild sensorineural hearing loss. There is therefore a need to incorporate regular audiologic assessment in the management protocol of the adult diabetic patients. </p
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Diabetes mellitus has been identified as major risk factor for developing severe COVID 19 complications. In this review article, the efforts were directed to provide insights and possible extent at which some diabetic pharmacological interventions may exacerbate COVID 19 or may not be idyllic options in COVID 19 patients. Articles reviewed were identified using Google scholar database, and search was done using English language. Anti-hyperglycaemic are associated with undesirable effects including episodes of hypoglycaemia, diarrhoea, lactacidosis and increased risks of cardiovascular and hepatic hazards. These undesirable effects associated with the anti-hyperglycaemic agents possess a threat of developing severe COVID19 complications Therefore, this calls for more studies to understand the extent of the risks these agents possess in diabetic COVID 19 patients. It is apparent that almost all the anti-hyperglycaemic agents have the potential to worsen COVID 19, despite their class. COVID 19 may limit the options in terms of available anti-hyperglycaemic agents which may not heighten the risk of developing severe COVID 19 complications. The research towards the discovery and development of new compounds and also new therapeutic targets for hyperglycaemia should be encouraged and welcome.
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Background Diabetes mellitus is a chronic metabolic disease that progresses to many microvascular complications. The phytoconstituents derived from herbs are thought to be important sources of anti-diabetic drug candidates. Mimosa pudica is one of such traditional herbal medicines having wide usage in treating diabetes mellitus. This study aims to validate the protective role of aqueous and alcoholic extracts of whole plant of Mimosa pudica in streptozotocin induced diabetic wistar albino rats. Methods The overnight fasted wistar rats were initially treated with nicotinamide followed by streptozotocin in order to induce type 2 diabetes. After 72h, the fasting blood glucose analysis was done and animals were further allocated to 5 different groups - Control group (no STZ administration); STZ control (with STZ administration); Group III (M. pudica ethanol extract 400 mg/kg; ME group); Group IV (M. pudica aqueous extract 400 mg/kg; MA); Group V (metformin 200 mg/kg). The treatment drugs were administered once a day for three weeks. The fasting blood glucose on the initial (day 0) and final (21st) day of the experiment was determined. Parameters like plasma insulin and hepato-renal function parameters, lipid peroxidation and antioxidants were estimated using standard kits. The animals were then sacrificed and liver tissues were collected for tissue analysis. Results Single-dose streptozotocin (STZ) significantly increased blood glucose level, HbA1c, liver enzymes and lipid peroxidation, whereas repeated administration of extracts of Mimosa pudica significantly indicated a strong protective effect in the treated animals. The cellular pool of reduced glutathione and subsequent reduction in the lipid peroxidation status and improved insulin production are also well-corroborated. The plant extracts have shown statistically significant reduction of oxidative stress thereby showing antioxidant property by restoring the enzymatic and non-enzymatic antioxidant molecules to nearly normal levels. Conclusion Overall, the study concludes that the phytoconstituents of M. pudica significantly controls the hyperglycaemic stress and glutathione depletion thereby provide therapeutically efficacious drug molecules for treating diabetes mellitus and its complications.
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Impaired insulin secretion plays a major role in the pathogenesis of type 2 diabetes mellitus, and progressive loss of beta-cell function is a pathophysiologic hallmark of type 2 diabetes. Recent science has elaborated on the role of the incretin hormones on beta-cell function and insulin secretion, as well as the role that incretin-based pharmacotherapies may have on glycemic control and beta-cell function, possibly altering the progressive loss of beta-cell function and possibly reversing/halting disease progression. However, incretin-based therapies may also have benefits extending beyond glycemic control and insulin secretion. In this review we examine some of those "beyond-glycemic" benefits, including presentation of data on weight reduction, blood pressure lowering, beneficial changes in the lipid profile, and improvements in myocardial and endothelial function. We investigate how those effects may help ameliorate the cardiovascular burden in patients with diabetes.
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Obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic steatohepatitis (NASH) can be complicated by cognitive impairment and neurodegeneration. Experimentally, high fat diet (HFD)-induced obesity with T2DM causes mild neurodegeneration with brain insulin resistance. Since ceramides are neurotoxic, cause insulin resistance, and are increased in T2DM, we investigated the potential role of ceramides as mediators of neurodegeneration in the HFD obesity/T2DM model. We pair-fed C57BL/6 mice with a HFD or control diet for 4-20 weeks and examined pro-ceramide gene expression in liver and brain and neurodegeneration in the temporal lobe. HFD feeding gradually increased body weight, but after 16 weeks, liver weight surged (P<0.001) due to lipid (triglyceride) accumulation (P<0.001), and brain weight declined (P<0.0001-Trend analysis). HFD feeding increased ceramide synthase, serine palmitoyl transferase, and sphingomyelinase expression in liver (P<0.05-P<0.001), but not brain. In HFD fed mice, temporal lobe levels of ubiquitin (P<0.001) and 4-hydroxynonenal (P<0.05 or P<0.01) increased, and tau, beta-actin, and choline acetyltransferase levels decreased (P<0.05-P<0.001) with development of NASH. In obesity, T2DM, or NASH, neurodegeneration with brain insulin resistance may be mediated by excess hepatic production of neurotoxic ceramides that readily cross the blood-brain barrier.
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Plasma free fatty acid (FFA) levels are elevated in obesity. FFAs cause insulin resistance in all major insulin target organs (skeletal muscle, liver, endothelial cells) and have emerged as a major link between obesity, the development of the metabolic syndrome, and atherosclerotic vascular disease. FFAs also produce low-grade inflammation in skeletal muscle, liver, and fat, which may contribute to cardiovascular events. The challenges for the future include the prevention or correction of obesity and elevated plasma FFA levels through methods that include decreased caloric intake and increased caloric expenditure, the development of methods to measure FFAs in small blood samples, and the development of efficient pharmacologic approaches to normalize increased plasma FFA levels.
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AMP-activated protein kinase (AMPK) is an energy sensor that regulates cellular metabolism. When activated by a deficit in nutrient status, AMPK stimulates glucose uptake and lipid oxidation to produce energy, while turning off energy-consuming processes including glucose and lipid production to restore energy balance. AMPK controls whole-body glucose homeostasis by regulating metabolism in multiple peripheral tissues, such as skeletal muscle, liver, adipose tissues, and pancreatic beta cells--key tissues in the pathogenesis of type 2 diabetes. By responding to diverse hormonal signals including leptin and adiponectin, AMPK serves as an intertissue signal integrator among peripheral tissues, as well as the hypothalamus, in the control of whole-body energy balance.
Article
Plasma free fatty acid (FFA) levels are elevated in obesity. FFA, by causing insulin resistance in muscle, liver, and endothelial cells, contributes to the development of type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD). The mechanism through which FFA induces insulin resistance involves intramyocellular and intrahepatocellular accumulation of triglycerides and diacylglycerol, activation of several serine/threonine kinases, reduction in tyrosine phosphorylation of the insulin receptor substrate (IRS)-1/2, and impairment of the IRS/phosphatidylinositol 3-kinase pathway of insulin signaling. FFA also produces low-grade inflammation in skeletal muscle and liver through activation of nuclear factor-kappaB, resulting in release of several proinflammatory and proatherogenic cytokines. Thus, elevated FFA levels (due to obesity or to high-fat feeding) cause insulin resistance in skeletal muscle and liver, which contributes to the development of T2DM, and produce low-grade inflammation, which contributes to the development of atherosclerotic vascular diseases and NAFLD.
Article
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.
Article
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