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Query: UMLS:C0011860 (type 2 diabetes)
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Type 2 diabetes mellitus and higher total plasma homocysteine concentrations are each associated with an increased incidence of cardiovascular disease and with diminished cognitive performance. Relations between homocysteine concentrations and cardiovascular disease incidence are stronger in the presence of type 2 diabetes mellitus. Therefore, we hypothesized that relations between homocysteine concentrations and cognitive performance would be stronger in the presence of type 2 diabetes. We related homocysteine concentrations and cognitive performance on the Mini-Mental State Examination in 817 dementia- and stroke-free participants of the Maine-Syracuse Study, 90 of whom were classified with type 2 diabetes mellitus. Regardless of statistical adjustment for age, sex, gender, vitamin co-factors (folate, vitamin B6, vitamin B12), cardiovascular disease risk factors, and duration and type of treatment for type 2 diabetes mellitus, statistically significant inverse associations between homocysteine concentrations and cognitive performance were observed for diabetic individuals. The weaker inverse associations between homocysteine concentrations and cognitive performance obtained for non-diabetic individuals were not robust to statistical adjustment for some covariates. Interactions between homocysteine concentrations and type 2 diabetes mellitus are observed such that associations between homocysteine and cognitive performance are stronger in the presence of diabetes.
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PMID:Homocysteine, type 2 diabetes mellitus, and cognitive performance: The Maine-Syracuse Study. 1619 5

We recently reported that in subjects with untreated type 2 diabetes mellitus, a 5-week diet of 20:30:50 carbohydrate-protein-fat ratio resulted in a dramatic decrease in 24-hour integrated glucose and total glycohemoglobin compared with a control diet of 55:15:30. Body weight, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and serum ketones were unchanged; insulin and nonesterified fatty acids were decreased. We now present data on other hormones and metabolites considered to be affected by dietary macronutrient changes. The test diet resulted in an elevated fasting plasma total insulin-like growth factor 1, but not growth hormone. Urinary aldosterone was unchanged; free cortisol was increased, although not statistically. Urinary pH and calcium were unchanged. Blood pressure, creatinine clearance, serum vitamin B12, folate, homocysteine, thyroid hormones, and uric acid were unchanged. Serum creatinine was modestly increased. Plasma alpha-amino nitrogen and urea nitrogen were increased. Urea production rate was increased such that a new steady state was present. The calculated urea production rate accounted for 87% of protein ingested on the control diet, but only 67% on the test diet, suggesting net nitrogen retention on the latter. The lack of negative effects, improved glucose control, and a positive nitrogen balance suggest beneficial effects for subjects with type 2 diabetes mellitus at risk for loss of lean body mass.
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PMID:The metabolic response to a high-protein, low-carbohydrate diet in men with type 2 diabetes mellitus. 1642 33

Genetics, oxidative stress: superoxide anion (O2*-) and hydrogen peroxide (H2O2), endothelial nitric oxide (eNO), lipid peroxides, anti-oxidants, endothelin, angiotensin converting enzyme (ACE) activity, angiotensinII, transforming growth factor-beta (TGF-beta), insulin, homocysteine, asymmetrical dimethyl arginine, proinflammatory cytokines: interleukin-6 (IL-6), tumor necrosis factor-a (TNF-alpha), C-reactive protein (hs-CRP), and long-chain polyunsaturated fatty acids (LCPUFAs), and activity of NAD(P)H oxidase have a role in human essential hypertension. There is a close interaction between endogenous molecules: eNO, endothelin, cytokines, and nutrients: folic acid, L-arginine, tetrahydrobiopterin (H4B), vitamin B6, vitamin B12, vitamin C, and LCPUFAs. Statins mediate some, if not all, of their actions through LCPUFAs, whereas these fatty acids (especially omega-3 fatty acids) suppress cyclo-oxygenase activity and the synthesis of pro-inflammatory cytokines, and activate parasympathetic nervous system, actions that reduce the risk of major vascular events. Some LCPUFAs form precursors to lipoxins and resolvins that have anti-inflammatory actions. Low-grade systemic inflammation seen in hypertension seems to have its origins in the perinatal period and availability of adequate amounts of LCPUFAs during the critical periods of brain growth prevents the development of hypertension. This indicates that preventive strategies aimed at decreasing the incidence of hypertension and its associated conditions such as atherosclerosis, type 2 diabetes, coronary heart disease (CHD), and cardiac failure in adulthood need to be instituted during the perinatal period if they are to be effective.
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PMID:Hypertension as a low-grade systemic inflammatory condition that has its origins in the perinatal period. 1671 19

Maternal micronutrient nutrition is an important determinant of size and body composition of the fetus. Maternal iron, iodine, calcium, folate, vitamin A, and vitamin C nutrition all influence offspring size. The Pune Maternal Nutrition Study was designed to study the relationship between maternal nutrition and fetal growth, size at birth, and postnatal growth. Maternal circulating folate and vitamin C concentrations predicted larger offspring size, while higher ferritin levels predicted smaller-sized babies. Subclinical vitamin B12 deficiency is common in India, especially in vegetarians, and children born to mothers with the lowest vitamin B12 but the highest folate status were the most adipose and the most insulin resistant. Furthermore, the relationship between maternal nutrition, fetal growth, and risk of type 2 diabetes and coronary heart disease appears to be much more complex than the simplistic postulates of the "fetal origins" hypothesis.
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PMID:Nutritional control of fetal growth. 1677 Sep 53

Major risk factors for cardiovascular diseases (myocardial infarction, angina pectoris, brain infarction) are age, male, smoking, high LDL-cholesterol, low HDL-cholesterol, high blood pressure, and diabetes mellitus. In Japanese population at large, healthy life-style to prevent cardiovascular diseases are; quit smoking, walking faster, saturated fat intake ranging 4.5-7 en%, lesser intake of trans fatty acids, cholesterol intake less 750 mg/day (male) and 600 mg/day (female), eat fish everyday, eat more folic acid, B6, and B12, eat grain, eat soybean products. However, it is not known whether this recommendation is also applied to NIDDM to prevent cardiovascular diseases. Based on reported evidences, to prevent cardiovascular diseases, NIDDM should quit smoking, eat fish everyday, and increase physical activity.
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PMID:[Lifestyle to prevent cardiovascular disease in NIDDM]. 1708

The aim of this study was to investigate the influence of homocysteine (hcy) levels on endothelial function by the method of brachial artery ultrasonography and their relation with microvascular complications in type 2 diabetes mellitus (T2DM) patients without macrovascular disease. Fifty-nine T2DM patients with a mean age of 53.4+/-8.6 years and diabetes duration of 8.1+/-6.2 years and 16 healthy controls with a mean age of 47+/-14.5 years were included in the study. Endothelialdependent and endothelium-independent flow-mediated dilatation (FMD) were evaluated via brachial artery ultrasonography. Fasting plasma glucose (FPG), glycosylated haemoglobin (A1c), lipid profile, hcy, B12 and folic acid levels were measured. Diabetic patients and control group individuals were compared with regard to the laboratory values and brachial artery vascular reactivity. Factors influencing endothelium-dependent FMD were investigated with linear regression analysis. Age, gender, body mass index, lipid profiles and hcy levels were similar in both groups (p>0.05). Endothelium-dependent FMD percentages were significantly lower in diabetics than in the control group (7.7+/-5.9 vs. 11.7+/-7.1%, p<0.05). Endothelial-independent FMD percentage was similar for both groups (p>0.05). The upper limit of the reference hcy value was found to be 12.6 micromol/l in the control group. In the diabetic group, hcy levels were high in 33 patients and normal in 26 patients. No difference was detected between the patients with high hcy levels and those with a normal level with regard to endothelium-dependent and endothelium-independent FMD values (p>0.05). Mean hcy levels were 16+/-1.7 and 13.3+/-4.3 micromol/l in T2DM patients with microvascular complication and those with no microvascular complication, respectively (p<0.05). Regression analysis revealed that the main factors influencing the endothelial-dependent FMD were FPG, total cholesterol (TC), triglycerides (TG) and high-density lipoprotein (HDL-C) levels (p<0.05, p=0.05, p=0.05, p=0.02, respectively). Hcy, folic acid and B12 values did not influence endothelium-dependent FMD (p>0.05). Diabetes duration and A1c levels were close to being significant although they did not reach statistical significance (p=0.07 and p=0.08 respectively). Hcy levels have no effect on endothelium-dependent and endothelium-independent FMD in T2DM patients without macrovascular complications. The influence of classical atherogenic factors (such as FPG, TC, TG and HDL-C levels) on endothelium functions, detected with endothelium-dependent FMD, is greater.
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PMID:The influence of homocysteine levels on endothelial function and their relation with microvascular complications in T2DM patients without macrovascular disease. 1753 Apr 70

The epidemic of obesity took off from about 1980 and in almost all countries has been rising inexorably ever since. Only in 1997 did WHO accept that this was a major public health problem and, even then, there was no accepted method for monitoring the problem in children. It was soon evident, however, that the optimum population body mass index is about 21 and this is particularly true in Asia and Latin America where the populations are very prone to developing abdominal obesity, type 2 diabetes and hypertension. These features are now being increasingly linked to epigenetic programming of gene expression and body composition in utero and early childhood, both in terms of fat/lean tissue ratios and also in terms of organ size and metabolic pathway regulation. New Indian evidence suggests that insulin resistance at birth seems linked to low birth weight and a higher proportion of body fat with selective B12 deficiency and abnormalities of one carbon pool metabolism potentially responsible and affecting 75% of Indians and many populations in the developing world. Biologically there are also adaptive biological mechanisms which limit weight loss after weight gain and thereby in part account for the continuing epidemic despite the widespread desire to slim. Logically, the burden of disease induced by inappropriate diets and widespread physical inactivity can be addressed by increasing physical activity (PA), but simply advocating more leisure time activity is unrealistic. Substantial changes in urban planning and diet are needed to counter the removal of any every day need for PA and the decades of misdirected food policies which with free market forces have induced our current 'toxic environment'. Counteracting this requires unusual policy initiatives.
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PMID:The epidemiology of obesity: the size of the problem. 1831 11

Alzheimer's disease, AD, is the most common form of dementia. AD initially targets memory and progressively destroys the mind. The brain atrophies as the neocortex suffers neuronal, synaptic, and dendritic losses, and the hallmark amyloid plaques and neurofibrillary tangles proliferate. Pharmacological management, at best, is palliative and transiently effective, with marked adverse effects. Certain nutrients intrinsic to human biochemistry (orthomolecules) match or exceed pharmacological drug benefits in double-blind, randomized, controlled trials, with superior safety. Early intervention is feasible because its heritability is typically minimal and pathological deterioration is detectable years prior to diagnosis. The syndrome amnestic mild cognitive impairment exhibits AD pathology and to date has frustrated attempts at intervention. The condition age-associated memory impairment is a nonpathological extreme of normal brain aging, but with less severe cognitive impairment than amnestic mild cognitive impairment. Age-associated memory impairment is a feasible target for early intervention against AD, beginning with the modifiable AD risk factors - smoking, hypertension, homocysteine, type 2 diabetes, insulin resistance, and obesity. Stress reduction, avoidance of toxins, and mental and physical exercise are important aspects of prevention. The diet should emphasize omega-3 fatty acids docosahexaenoic acid and eicosapentaenoic acid; flavonoids and other antioxidant nutrients; and B vitamins, especially folate, B6 and B12. Dietary supplementation is best focused on those proven from randomized, controlled trials: the phospholipids phosphatidylserine and glycerophosphocholine, the energy nutrient acetyl-L-carnitine, vitamins C and E, and other antioxidants. A comprehensive integrative strategy initiated early in cognitive decline is the most pragmatic approach to controlling progression to Alzheimer's disease.
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PMID:Alzheimer's disease, amnestic mild cognitive impairment, and age-associated memory impairment: current understanding and progress toward integrative prevention. 1859 Mar 47

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

Nearly 20 years ago, it was discovered that low birthweight was associated with an increased risk of adult diabetes and cardiovascular disease (CVD). This led to the hypothesis that exposure to undernutrition in early life increases an individual's vulnerability to these disorders, by 'programming' permanent metabolic changes. Implicit in the programming hypothesis is that improving the nutrition of girls and women could prevent common chronic diseases in future generations. Research in India has shown that low birthweight children have increased CVD risk factors, and a unique birth cohort in Delhi has shown that low infant weight, and rapid childhood weight gain, increase the risk of type 2 diabetes. Progress has been made in understanding the role of specific nutrients in the maternal diet. In the Pune Maternal Nutrition Study, low maternal vitamin B12 status predicted increased adiposity and insulin resistance in the children, especially if the mother was folate replete. It is not only maternal undernutrition that causes problems; gestational diabetes, a form of foetal overnutrition (glucose excess), is associated with increased adiposity and insulin resistance in the children, highlighting the adverse effects of the 'double burden' of malnutrition in developing countries, where undernutrition and overnutrition co-exist. Recent intervention studies in several developing countries have shown that CVD risk factors in the offspring can be improved by supplementing undernourished mothers during pregnancy. Results differ according to the population, the intervention and the post-natal environment. Ongoing studies in India and elsewhere seek to understand the long-term effects of nutrition in early life, and how best to translate this knowledge into policies to improve health in future generations.
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PMID:Maternal nutrition: effects on health in the next generation. 2009 Jan 13


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