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Metabolic syndrome (MS) is a common condition strongly associated with the development of type 2 diabetes and coronary heart disease (CHD). High triglycerides (TG) and low high density lipoprotein cholesterol (HDL-C) often occur together and represent the fundamental dyslipidemia of patients with MS. This abnormal lipoprotein profile is a major risk factor for premature cardiovascular disease. This review briefly discusses new findings on structure and functions of HDL in the atherogenic dyslipidemic condition known as MS. While the knowledge of the association between HDL-C and CHD began with the observation of an inverse relationship between HDL-C values and CHD risk, information in recent years shows the important role of HDL function in the pathogenesis of atherosclerosis. HDL particles are heterogeneous in structure, intravascular metabolism and antiatherogenic activity. Reductions in HDL-C concentrations, as seen in MS, are frequently associated with an abnormal HDL subclass distribution, altered HDL chemical composition, reduced antiinflamatory and antioxidative properties, and low capacity to promote cholesterol efflux. Deficiency of HDL particle number and attenuated antiaterogenic activity favor accelerated atherosclerosis. These data justify renewed emphasis on low HDL-C as a major risk factor in the prevention and treatment of CHD. Pharmacological interventions that increase HDL-C can also improve the quality and biological activities of HDL particles. Fibrates, nicotinic acid, cholesteryl ester transfer protein inhibitors, and reconstituted HDL are being investigated. Patients with MS constitute a high risk group that would particularly benefit from intervention to rise HDL-C.
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PMID:[Some physiopathologic features of metabolic syndrome]. 1893 96

Epidemiological studies suggest that the perinatal environment can predispose human offspring to develop obesity and type 2 diabetes. Animal models provide a means of assessing the consequences of manipulating the perinatal environment in ways that cannot be done in humans. During the gestational period, maternal malnutrition, obesity, type 1 and type 2 diabetes, and psychological and pharmacological stressors can all promote, while early-onset exercise can ameliorate, offspring obesity and diabetes, especially in genetically predisposed offspring. Many of these perinatal manipulations are associated with reorganization of the central neural pathways which regulate food intake, energy expenditure, and storage in ways that enhance the development of obesity and diabetes in offspring. Both leptin and insulin have strong neurotrophic properties, so altered availability of either during the perinatal period can underlie some of these adverse developmental changes. Because perinatal manipulations can permanently alter the systems which regulate energy homeostasis, it behooves us to identify the responsible factors as a means of stemming the tide of the emerging worldwide obesity epidemic.
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PMID:Epigenetic influences on food intake and physical activity level: review of animal studies. 1903 14

It has recently been increasingly recognised that disturbed intra-uterine development may impact on renal and cardiovascular risk in adult life, e.g. albuminuria and chronic kidney disease, hypertension, type 2 diabetes or cardiovascular events. According to Barker's hypothesis, when resources in utero are restricted, their allocation to the development of the kidney and pancreatic islets is restricted to guarantee appropriate development of the brain and heart. The underlying epigenetic mechanisms involve modification of gene expression by altered DNA methylation and histone acetylation as well as by allocation of stem cells. The result of this trade-off between the brain and kidney during organogenesis is a diminished number of nephrons ('nephron underdosing') which predisposes to albuminuria and risk of chronic kidney disease, as well as hypertension. In parallel, changed appetite centres, insulin resistance and beta-cell development predispose to obesity, metabolic syndrome and type 2 diabetes and the resulting renal sequelae. Numerous factors may trigger intra-uterine restriction of fetal growth, such as uterine underperfusion, maternal malnutrition, hyperglycaemia and hyperinsulinaemia of the mother, smoking or medications.
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PMID:Prenatal causes of kidney disease. 1916 17

Metabolic syndrome (MetS) is defined as a cluster of risk factors for type 2 diabetes and cardiovascular disease; it is also an independent risk factor for developing chronic kidney disease (CKD) in the general population. Therefore, CKD has many similarities and associations with MetS, and the individual risk factors constituting MetS-especially insulin resistance and glucose intolerance, hypertension, dyslipidemia, and obesity-are also common features of the early stages of CKD. In the later stages of CKD, uremia per se and uremic complications such as fluid retention, protein-energy wasting, inflammation, and oxidative stress further contribute to an increase in the prevalence of MetS in CKD patients. In addition, PD patients exposed to glucose-based PD fluids have an increased risk of developing metabolic complications. The broad use of MetS in clinical research has raised the awareness of the public and of individual patients concerning the value of lifestyle interventions. However, the definition and pathogenesis of MetS are still debated, and no standardized definition nor proven prognostic value has been established for MetS as a cluster of risk factors for diabetes or cardiovascular disease in PD patients. Furthermore, considering the paradoxical associations of some of the risk factors in MetS with decreased mortality, another set of risk factors-those specific to patients with uremia (for example, inflammation and malnutrition)-and the appropriate cut-off levels to individual MetS risk factors should be taken account at the same time. Also, the benefit of interventions targeting these risk factors should be clarified in further clinical studies.
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PMID:Definition of metabolic syndrome in peritoneal dialysis. 1927 Feb 3

The fetal origins hypothesis, proposes that non-communicable diseases including coronary heart disease, type 2 diabetes and hypertension originate through the responses of a fetus to undernutrition, that permanently change the structure and function of the body. Associations between low birthweight and disease in later life have been widely studied in Europe and the USA. Studies in southern India have shown that babies who are short and fat tend to become insulin deficient and have high rates of non-insulin dependent diabetes. These findings have important public health implications as it suggests that associations with body size at birth underestimate the contribution of intrauterine development to later disease, and also, that while the primary prevention of coronary heart disease and non-insulin dependent diabetes may ultimately depend on changing the body composition and diets of young women. Therefore, more immediate benefit may come from preventing imbalances between prenatal and postnatal growth among children. The basic premise of the thrifty gene hypothesis is that certain populations may have genes that determine increased fat storage, which in times of famine represent a survival advantage, but in a modern environment result in obesity and type 2 diabetes. The fetal origins theory is of greatest relevance to the developing world and the implications of this work for global health are enormous. To reduce chronic diseases, we need to understand how the human fetus is nourished and how malnutrition changes its physiology and metabolism, so that interventions be implemented to limit the damage. The challenge for the next decade must be to discover the cellular and molecular mechanisms giving rise to these associations. If this aim is accomplished, it might be possible to devise strategies to reduce the impact of these disabling chronic and expensive diseases.
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PMID:Markers of fetal onset adult diseases. 1927 69

Here we explore whether there is any evidence that the rapid development of the obesity epidemic in emerging nations, and its unusual coexistence with malnutrition, may have evolutionary origins that make such populations especially vulnerable to the obesogenic conditions accompanying the nutrition transition. It is concluded that any selection of so-called 'thrifty genes' is likely to have affected most races due to the frequency and ubiquity of famines and seasonal food shortages in ancient populations. Although it remains a useful stimulus for research, the thrifty gene hypothesis remains a theoretical construct that so far lacks any concrete examples. There is currently little evidence that the ancestral genomes of native Asian or African populations carry particular risk alleles for obesity. Interestingly, however, there is evidence that a variant allele of the FTO gene that favors leanness may be less active in Asians or Africans. There is also some evidence that Caucasians may be less prone to developing type 2 diabetes mellitus than other races suggesting that there has been recent selection of protective alleles. In the near future, recently developed statistical methods for comparing genome-wide data across populations are likely to reveal or refute the presence of any thrifty genes and might indicate mechanisms of vulnerability.
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PMID:Obesity in emerging nations: evolutionary origins and the impact of a rapid nutrition transition. 1934 67

The coexistence of intrauterine and neonatal malnutrition and the development of obesity, type 2 diabetes and related comorbidities have been confirmed in a number of studies in humans and animal models. Data from studies in animals suggest that epigenetic changes as a result of altered methylation of the genomic DNA may be responsible for such metabolic patterning. Methionine, an essential amino acid, plays a critical role in the methyltranferases involved in the methylation by providing the one-carbon units via the methionine transmethylation cycle. Because of its interaction with a number of vitamins (B12, folate, pyridoxine), its regulation by hormones, i.e. insulin and glucagon, and by the changes in redox state, methionine metabolism is effected by nutrient and environmental influences and by altered physiological states. In the present review the impact of human pregnancy, dietary protein restriction and fatty liver disease on methionine metabolism is discussed. The role of methionine in metabolic programming in a commonly used model of intrauterine growth retardation and in propagation of fatty liver disease is briefly described.
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PMID:Metabolism of methionine in vivo: impact of pregnancy, protein restriction, and fatty liver disease. 1934 72

Globally an estimated 20 million infants are born with low birthweight (LBW), of those over 18 million are born in developing countries. These LBW infants are at a disproportionately higher risk of mortality, morbidity, poor growth, impaired psychomotor and cognitive development as immediate outcomes, and are also disadvantaged as adults due to their greater susceptibility to type 2 diabetes, hypertension and coronary heart disease. Maternal malnutrition prior to and during pregnancy manifested by low bodyweight, short stature, inadequate energy intake during pregnancy and coexisting micronutrient deficiency are considered major determinants in developing countries where the burden is too high. LBW is a multifactorial outcome and its prevention requires a lifecycle approach and interventions must be continued for several generations. So far, most interventions are targeted during pregnancy primarily due to the increased nutritional demand and aggravations of already existing inadequacy in most women. Several individually successful interventions during pregnancy include balanced protein energy supplementation, several single micro-nutrients or more recently a mix of multiple micronutrients. Nutrition education has been successful in increasing the dietary intake of pregnant women but has had no effect on LBW. The challenge is to identify a community-specific intervention package. Current evidence supports intervention during pregnancy with increased dietary intakes including promotions of foods rich in micronutrients and micronutrient supplementation, preferably with a multiple micronutrient mix. Simultaneously a culturally appropriate educational component is required to address misconceptions about diet during pregnancy and childbirth including support for healthy pregnancy with promotion of antenatal and perinatal care services. While further research is needed to identify more efficacious interventions, an urgent public health priority would be to select and implement an optimal mix of interventions to avert the immediate adverse consequences of LBW and to prevent the impending epidemic of type 2 diabetes, hypertension and coronary heart disease which are negatively associated with LBW.
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PMID:Prevention of low birthweight. 1934 78

Epidemiological studies suggest that maternal undernutrition, obesity and diabetes during gestation and lactation can all produce obesity in human offspring. Animal models provide a means of assessing the independent consequences of altering the pre- vs postnatal environments on a variety of metabolic, physiological and neuroendocrine functions, which lead to the development of offspring obesity, diabetes, hypertension and hyperlipidemia. During the gestational period, maternal malnutrition, obesity, type 1 and type 2 diabetes, and psychological and pharmacological stressors can all promote offspring obesity. Normal postnatal nutrition can sometimes reduce the adverse effect of some of these prenatal factors, but may also exacerbate the development of obesity and diabetes in offspring of dams that are malnourished during gestation. The genetic background of the individual is also an important determinant of outcome when the perinatal environment is perturbed. Individuals with an obesity-prone genotype are more likely to be adversely affected by factors such as maternal obesity and high-fat diets. Many perinatal manipulations are associated with reorganization of the central neural pathways which regulate food intake, energy expenditure and storage in ways that enhance the development of obesity and diabetes in offspring. Both leptin and insulin have strong neurotrophic properties so that an excess or an absence of either of them during the perinatal period may underlie some of these adverse developmental changes. As perinatal manipulations can permanently and adversely alter the systems that regulate energy homeostasis, it behooves us to gain a better understanding of the factors during this period that promote the development of offspring obesity as a means of stemming the tide of the emerging worldwide obesity epidemic.
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PMID:Synergy of nature and nurture in the development of childhood obesity. 1936 9

Population aging is progressing rapidly in many industrialized countries. The United States population aged 65 and over is expected to double in size within the next 25 years. In sedentary people eating Western diets aging is associated with the development of serious chronic diseases, including type 2 diabetes mellitus, cancer and cardiovascular diseases. About 80% of adults over 65 years of age have at least one chronic disease, and 50% have at least two chronic diseases. These chronic diseases are the most important cause of illness and mortality burden, and they have become the leading driver of healthcare costs, constituting an important burden for our society. Data from epidemiological studies and clinical trials indicate that many age-associated chronic diseases can be prevented, and even reversed, with the implementation of healthy lifestyle interventions. Several recent studies suggest that more drastic interventions (i.e. calorie restriction without malnutrition and moderate protein restriction with adequate nutrition) may have additional beneficial effects on several metabolic and hormonal factors that are implicated in the biology of aging itself. Additional studies are needed to understand the complex interactions of factors that regulate aging and age-associated chronic disease.
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PMID:Modulating human aging and age-associated diseases. 1936 77


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