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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is a worldwide epidemic with multiple obesity-associated health problems including type 2 diabetes, hypertension, and cardiovascular disease. Adipose tissue serves as a fuel storage depot, but also plays a pivotal role in homeostasis of energy expenditure, appetite regulation, glucose regulation, and immunity. Both genetics and environment play important roles in adipose tissue function and dysfunction. Obesity represents an abnormal accumulation of adipose tissue resulting from chronic overnutrition and reduced physical activity. The nature of this increased accumulation of fat tissue, whether hyperplasia or hypertrophy, local or ectopic, is associated with deleterious perturbations including excess fatty acid secretion, increased production of inflammatory cytokines, and abnormal adipocyte hormone signaling resulting in insulin resistance. In the setting of obesity, insulin resistance and chronic inflammation is postulated to play a role in development of type 2 diabetes and other obesity-related comorbidities including obstructive sleep apnea, hepatic steatosis, polycystic ovarian syndrome, hypertension and cardiovascular disease. Although the exact mechanism of these relationships are complex and not completely understood, the ability to store and limit fatty acid deposition to adipose tissue is a common component to remaining insulin sensitive, controlling the inflammatory cascade and reducing the risk of developing obesity-related comorbidities.
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PMID:Obesity and the development of type 2 diabetes: the effects of fatty tissue inflammation. 2143 93

Chronic overnutrition and consequential visceral obesity is associated with a cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus. Moreover, individuals who have a triad of hypertension, dysglycemia, and elevated triglycerides along with reduced high-density lipoprotein cholesterol have a greater residual cardiovascular risk even after factoring for the traditional risk factors such as age, smoking, diabetes, and elevated low-density lipoprotein cholesterol. In our previous study we demonstrated that TRC150094, when administered to rats receiving a high-fat diet, stimulated mitochondrial fatty acid oxidation (FAO) and reduced visceral adiposity, opening an interesting perspective for a possible clinical application. In the present study, oral administration of TRC150094 to obese Zucker spontaneously hypertensive fatty rats (obese ZSF1) improved glucose tolerance and glycemic profile as well as attenuated a rise in blood pressure. Obese ZSF1 rats treated with TRC150094 also showed reduced hepatic steatosis, reduced progression of nephropathy, and improved skeletal muscle function. At the cellular level, TRC150094 induced a significant increase in mitochondrial respiration as well as an increased FAO in liver and skeletal muscle, ultimately resulting in reduced hepatic as well as total body fat accumulation, as evaluated by magnetic resonance spectroscopy and magnetic resonance imaging, respectively. If reproduced in humans, these results could confirm that TRC150094 may represent an attractive therapeutic agent to counteract multiple residual cardiovascular risk components.
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PMID:TRC150094 attenuates progression of nontraditional cardiovascular risk factors associated with obesity and type 2 diabetes in obese ZSF1 rats. 2144 17

The increasing prevalence of overnutrition and reduced activity has led to a worldwide epidemic of obesity. In many cases, this is associated with insulin resistance, an inability of the hormone to direct its physiological actions appropriately. A number of disease states accompany insulin resistance such as type 2 diabetes mellitus, the metabolic syndrome, and non-alcoholic fatty liver disease. Though the pathways by which insulin controls hepatic glucose output have been of intense study in recent years, considerably less attention has been devoted to how lipid metabolism is regulated. Thus, both the proximal signaling pathways as well as the more distal targets of insulin remain uncertain. In this review, we consider the signaling pathways by which insulin controls the synthesis and accumulation of lipids in the mammalian liver and, in particular, how this might lead to abnormal triglyceride deposition in liver during insulin-resistant states.
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PMID:Insulin signaling to hepatic lipid metabolism in health and disease. 2159 35

Persistently elevated oxidative stress and inflammation precede or occur during the development of type 1 or type 2 diabetes mellitus and precipitate devastating complications. Given the rapidly increasing incidence of diabetes mellitus and obesity in the space of a few decades, new genetic mutations are unlikely to be the cause, instead pointing to environmental initiators. A hallmark of contemporary culture is a preference for thermally processed foods, replete with pro-oxidant advanced glycation endproducts (AGEs). These molecules are appetite-increasing and, thus, efficient enhancers of overnutrition (which promotes obesity) and oxidant overload (which promotes inflammation). Studies of genetic and nongenetic animal models of diabetes mellitus suggest that suppression of host defenses, under sustained pressure from food-derived AGEs, may potentially shift homeostasis towards a higher basal level of oxidative stress, inflammation and injury of both insulin-producing and insulin-responsive cells. This sequence promotes both types of diabetes mellitus. Reducing basal oxidative stress by AGE restriction in mice, without energy or nutrient change, reinstates host defenses, alleviates inflammation, prevents diabetes mellitus, vascular and renal complications and extends normal lifespan. Studies in healthy humans and in those with diabetes mellitus show that consumption of high amounts of food-related AGEs is a determinant of insulin resistance and inflammation and that AGE restriction improves both. This Review focuses on AGEs as novel initiators of oxidative stress that precedes, rather than results from, diabetes mellitus. Therapeutic gains from AGE restriction constitute a paradigm shift.
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PMID:AGE restriction in diabetes mellitus: a paradigm shift. 2161 Jun 89

Type 2 diabetes is a global public health crisis that threatens the economies of all nations, particularly developing countries. Fueled by rapid urbanization, nutrition transition, and increasingly sedentary lifestyles, the epidemic has grown in parallel with the worldwide rise in obesity. Asia's large population and rapid economic development have made it an epicenter of the epidemic. Asian populations tend to develop diabetes at younger ages and lower BMI levels than Caucasians. Several factors contribute to accelerated diabetes epidemic in Asians, including the "normal-weight metabolically obese" phenotype; high prevalence of smoking and heavy alcohol use; high intake of refined carbohydrates (e.g., white rice); and dramatically decreased physical activity levels. Poor nutrition in utero and in early life combined with overnutrition in later life may also play a role in Asia's diabetes epidemic. Recent advances in genome-wide association studies have contributed substantially to our understanding of diabetes pathophysiology, but currently identified genetic loci are insufficient to explain ethnic differences in diabetes risk. Nonetheless, interactions between Westernized diet and lifestyle and genetic background may accelerate the growth of diabetes in the context of rapid nutrition transition. Epidemiologic studies and randomized clinical trials show that type 2 diabetes is largely preventable through diet and lifestyle modifications. Translating these findings into practice, however, requires fundamental changes in public policies, the food and built environments, and health systems. To curb the escalating diabetes epidemic, primary prevention through promotion of a healthy diet and lifestyle should be a global public policy priority.
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PMID:Globalization of diabetes: the role of diet, lifestyle, and genes. 2161 9

Epidemiological studies have suggested that metabolic programming is one of the critical factors contributing to the etiology of obesity as well as concurrent increase in related chronic diseases (e.g., type 2 diabetes and cardiovascular disease). Metabolic programming is the phenomenon whereby a nutritional stress/stimulus applied during critical periods of early development permanently alters an organism's physiology and metabolism, the consequences of which are often observed much later in life. The idea of metabolic programming originated from the fetal origins hypothesis proposed by Barker in which he suggested that disproportionate size at birth of the newborn due to an adverse intrauterine environment correlated well with an increased risk of adult-onset ill health outcomes (type 2 diabetes, hypertension, and cardiovascular disease). The fetal origins hypothesis, proposed by Barker, suggests that adequate nutrition during fetal development is critical. Overnutrition is a form of malnutrition that has increased in the United States over the past several decades in which nutrients are oversupplied relative to the amounts required for normal growth, development, and metabolism. Evidence for the effects of maternal obesity and overnutrition on metabolic programming is reviewed during critical prenatal, perinatal, and postnatal periods.
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PMID:Metabolic imprinting by prenatal, perinatal, and postnatal overnutrition: a review. 2176 66

There is now clear evidence from population-based and experimental animal studies that maternal obesity and maternal overnutrition, particularly excessive intake of high-fat and high-sugar diets, is associated with an increased risk of obesity and type 2 diabetes in the offspring. Whilst the physiological reasons for this association are still not fully understood, one of the key pathways appears to be the ability of exposure to an oversupply of energy, fat and sugar during critical windows of development to program an increased food intake in the offspring. This review will focus on our current understanding of the programming of food intake, with a focus on the importance of the maternal diet. Specifically, we will discuss how exposure to an increased energy supply before birth and in early infancy, and/or increased maternal intake of palatable foods alters the development of the systems regulating appetite and food preferences, and how these changes interact to promote excess consumption and thus predispose the offspring to weight gain and obesity.
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PMID:The fetal origins of obesity: early origins of altered food intake. 2183 Oct 32

The fetal origin hypothesis of adult cardiovascular diseases, type 2 diabetes, hypertension and dyslipidemia in persons born with low birthweight, independently of their extrauterine risk factors, has been well established in the last decade of the twentieth century. However, mechanisms responsible for this relationship are still under investigation. Insulin resistance resulting from the restriction of intrauterine development of skeletal muscles and other organs is considered as the most important cause of metabolic disturbances and their cardiovascular complications in adult subjects born with intrauterine growth retardation (IUGR). Decline of insulin secretion, overactivation of the hypothalamo-pituitary-adrenal axis, reduced glucose uptake in the liver and raised lipid oxidation in the muscles may also explain this association. On the other hand, abnormal vascular development , increased activity of the sympathetic nervous system, defective endothelial function and/or impaired renal function in growth restricted newborns may contribute to hypertension in their later life. With respect to maternal conditions and life-style factors that may increase cardiovascular risk in adult offspring born with IUGR, the most consistent results concern pregnancy induced hypertension, preeclampsia, undernutrition, smoking during pregnancy, hypercholesterolemia, inflammation and/or enhanced glucocorticoid secretion. Macrosomia of the newborn, a frequent sequel to maternal diabetes and/or obesity, also increases the risk of diabetes and cardiovascular diseases in adulthood. Maternal overnutrition, and particularly high fat and sugar intake, seem to play a key role in fetal programming of cardiovascular risk in subjects born with macrosomia. Epigenetic imprinting underlies the described pathomechanisms. The presented associations are illustrated, among others, with the results of studies performed by the authors of this review.
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PMID:Fetal development and risk of cardiovascular diseases and diabetes type 2 in adult life. 2200 75

The role of local tissue renin-angiotensin system (tRAS) activation in the cardiorenal metabolic syndrome (CRS) and type 2 diabetes mellitus (T2DM) is not well understood. To this point, we posit that early redox stress-mediated injury to tissues and organs via accumulation of excessive reactive oxygen species (ROS) and associated wound healing responses might serve as a paradigm to better understand how tRAS is involved. There are at least five common categories responsible for generating ROS that may result in a positive feedback ROS-tRAS axis. These mechanisms include metabolic substrate excess, hormonal excess, hypoxia-ischemia/reperfusion, trauma, and inflammation. Because ROS are toxic to proteins, lipids, and nucleic acids they may be the primary instigator, serving as the injury nidus to initiate the wound healing process. Insulin resistance is central to the development of the CRS and T2DM, and there are now thought to be four major organ systems important in their development. In states of overnutrition and tRAS activation, adipose tissue, skeletal muscle (SkM), islet tissues, and liver (the quadrumvirate) are individually and synergistically related to the development of insulin resistance, CRS, and T2DM. The obesity epidemic is thought to be the driving force behind the CRS and T2DM, which results in the impairment of multiple end-organs, including the cardiovascular system, pancreas, kidney, retina, liver, adipose tissue, SkM, and nervous system. A better understanding of the complex mechanisms leading to local tRAS activation and increases in tissue ROS may lead to new therapies emphasizing global risk reduction of ROS resulting in decreased morbidity and mortality.
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PMID:Possible Mechanisms of Local Tissue Renin-Angiotensin System Activation in the Cardiorenal Metabolic Syndrome and Type 2 Diabetes Mellitus. 2209 55

A substantial body of evidence suggests that an abnormal intrauterine milieu elicited by maternal metabolic disturbances as diverse as undernutrition, placental insufficiency, diabetes or obesity, may program susceptibility in the fetus to later develop chronic degenerative diseases, such as obesity, hypertension, cardiovascular diseases and diabetes. This paper examines the developmental programming of glucose intolerance/diabetes by disturbed intrauterine metabolic condition experimentally obtained in various rodent models of maternal protein restriction, caloric restriction, overnutrition or diabetes, with a focus on the alteration of the developing beta-cell mass. In most of the cases, whatever the type of initial maternal metabolic stress, the beta-cell adaptive growth which normally occurs during gestation, does not take place in the pregnant offspring and this results in the development of gestational diabetes. Therefore gestational diabetes turns to be the ultimate insult targeting the offspring beta-cell mass and propagates diabetes risk to the next generation again. The aetiology and the transmission of spontaneous diabetes as encountered in the GK/Par rat model of type 2 diabetes, are discussed in such a perspective. This review also discusses the non-genomic mechanisms involved in the installation of the programmed effect as well as in its intergenerational transmission.
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PMID:Early-life origins of type 2 diabetes: fetal programming of the beta-cell mass. 2211 Apr 71


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