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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our review focuses on low density lipoprotein (LD lipoprotein) and very low density lipoprotein (VLD lipoprotein) in their roles as transporters of cholesterol and triglyceride and as factors contributing to premature arteriovascular disease. We describe the clinical manifestations of the common, primary hyperlipoproteinemias--that is, hyper-beta-lipoproteinemia, combined hyperlipoproteinemia, hyper-pre-beta-lipoproteinemia, and sporadic hyperlipoproteinemia--and discuss the variations in lipoprotein structure and metabolism that occur in these diseases. Based on an understanding of the physiologic control of lipoprotein metabolism, it is possible for the physician to alter the concentrations of LD lipoprotein and VLD lipoprotein by selecting a course of therapy appropriate to the specific disease. We describe the effects of obesity, diet, insulin, ethanol, estrogens, and the drugs clofibrate, nicotinic acid, and cholestyramine.
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PMID:The common hyperlipoproteinemias: an understanding of disease mechanisms and their control. 18 30

Patients with diabetes mellitus are at increased risk of morbidity and mortality from macrovascular disease manifesting as coronary heart disease, cerebrovascular accidents, and peripheral vascular disease. Increased frequency of dyslipidemia, hyperglycemia, obesity, hypertension, and associated nephropathy may contribute to accelerated atherogenesis in diabetic patients. Therefore, besides intensive control of hyperglycemia, management of dyslipidemia, hypertension, and obesity should also be emphasized in diabetic patients. Those who smoke should be strongly encouraged to quit smoking. Besides attempts to achieve normal levels of plasma lipoproteins, consideration also should be given to normalization of compositional abnormalities of various lipoproteins in patients with diabetes mellitus. The therapeutic goals for cholesterol reduction should be lower in diabetic patients than nondiabetic subjects. The first step is to achieve good metabolic control of diabetes mellitus by diet, exercise, and weight reduction and, if needed, with sulfonylureas or insulin therapy. Because most of the patients with insulin-dependent diabetes mellitus achieve normal levels of plasma lipoproteins with intensive insulin therapy, lipid-lowering medications are rarely needed. In patients with non-insulin-dependent diabetes mellitus, however, dyslipidemia often persists despite good glycemic control. Lipid-lowering medications should be considered in such patients. Because nicotinic acid can cause marked deterioration in glycemic control, and bile acid-binding resins may accentuate hypertriglyceridemia, these agents are less desirable for use by diabetic patients. Inhibitors of hydroxymethylglutaryl coenzyme A reductase may be preferred in patients with elevated LDL cholesterol and mld hypertriglyceridemia. For diabetic patients with marked hypertriglyceridemia, however, fibric acid derivatives should be the drug of choice.
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PMID:Lipid-lowering therapy and macrovascular disease in diabetes mellitus. 152 29

Coronary heart disease is the leading cause of death among patients with non-insulin-dependent diabetes mellitus (NIDDM). NIDDM patients have a high frequency of dyslipidemia, which along with obesity, hypertension, and hyperglycemia may contribute significantly to accelerated coronary atherosclerosis. Because risk factors for coronary heart disease are additive and perhaps multiplicative, even mild degrees of dyslipidemia may enhance coronary heart disease risk. Therefore, therapeutic strategies for management of NIDDM should give equal emphasis to controlling hyperglycemia and dyslipidemia. The National Cholesterol Education Program recently issued guidelines for treatment of hyperlipidemia in adults including diabetic patients. Because of the unique features of diabetic dyslipidemia, however, we suggest that certain modifications in these guidelines be made to meet specific needs of diabetic patients. For example, therapeutic goals for serum cholesterol reduction should be lower in diabetic patients than in nondiabetic subjects. Particular emphasis should be given to weight reduction in NIDDM patients. In some diabetic patients, monounsaturated fatty acids may be a better replacement for saturated fatty acids than carbohydrates. The target for cholesterol lowering should include both very-low-density lipoprotein and low-density lipoprotein (LDL) (non-high-density lipoprotein) rather than LDL alone. To obtain a substantial reduction of cholesterol levels, drug therapy may be required in many patients. However, first-line drugs for nondiabetic patients (nicotinic acid and bile acid sequestrants) may be less desirable in NIDDM patients than hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors and even fibric acids. In fact, HMG CoA reductase inhibitors may be the drugs of choice for NIDDM patients with elevated LDL cholesterol and borderline hypertriglyceridemia, whereas gemfibrozil appears preferable for NIDDM patients with severe hypertriglyceridemia.
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PMID:Management of dyslipidemia in NIDDM. 219 Jul 70

Insulin resistance is frequently observed in obese subjects. The present work was initiated to study its relationship with the increased lipid metabolism generally observed in obesity. A first group of five obese subjects (146 +/- 10% of their ideal body weight [IBW] with normal glucose tolerance was submitted to a 75-g oral glucose tolerance test (OGTT) as a control and during an intralipid infusion (20% fat emulsion, 1 mL/min, started 90 minutes prior to the glucose load). Lipid and glucose oxidation were measured by continuous indirect calorimetry. The significant rise over control conditions in both plasma FFA and lipid oxidation rate during the lipid infusion was accompanied by a marked decrease in glucose tolerance (two hours venous plasma glucose: 151 +/- 12 during intralipid infusion v 110 +/- 3 mg/dL, P less than .01) together with a rise of the plasma insulin curve. Glucose oxidation was significantly decreased. A second group of five obese subjects (146 +/- 7% of their IBW) with impaired glucose tolerance was submitted to a similar OGTT, as a control, and during an infusion of beta-pyridyl-carbinol, a nicotinic acid derivative, to lower FFA. Both plasma FFA and lipid oxidation rates were decreased already prior to the OGTT. The previously impaired glucose tolerance was normalized (two hours venous plasma glucose: 129 +/- 13 during the beta-pyridyl-carbinol infusion v 172 +/- 7 mg/dL, P less than .01), and the insulin curve lowered. Glucose oxidation was increased during the early phase of the OGTT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolic factors in the insulin resistance in human obesity. 354 14

Nutritional status (anthropometry, food habits, thiamin and riboflavin status) has been evaluated in 136 (70 males and 66 females) free living healthy elderly individuals (age range 65-69 yrs) from the district of San Carlo Arena that can be considered representative of the sociocultural and economic level of the city of Naples. By assuming as reference values those of middle aged individuals, 50 percent of elderly men and 85 percent of elderly women showed different degree of excess body fat. As far as food habits are concerned legumes, vegetables and fruit daily intake was quite high whilst alcohol consumption was low. Furthermore milk and eggs intake was low and infrequent. Although prevalence of excess body weight was high, total daily energy intake was found to be equal or slightly above dietary recommendations for the elderly. Diet composition showed a high protein intake whilst CHO and fat intake was slightly below recommendations. Micronutrients' intake was insufficient for calcium in 10 percent of both males and females and for iron in 20 percent of men and 40 percent of women. Niacin intake was low in about 50 percent of both men and women. Thiamin nutritional status was found low in 20 percent of men and women and riboflavin status in 40 percent of men and 20 percent of women. In conclusion obesity and overweight are very frequent in an urbanized sample of free living healthy elderly individuals of Naples. On the other hand serum calcium and iron and some vitamin deficiency is not uncommon. The composition of the diet seems to be also poor in some micronutrients.
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PMID:Nutritional status of the elderly in Naples. 365 13

An increased supply of FFAs for oxidation leads to a reduced rate of glucose oxidation and interferes with the inhibitory action of insulin on hepatic glucose production. Available evidence indicates that in humans skeletal muscle is a site for such substrate competition, which involves both pyruvate oxidation and glycogen synthesis. The insulin resistance of obesity is thought to be mostly of metabolic origin, and fully reversible. A reduction in FFA supply by weight reduction can, however, reverse this defect. The insulin resistance associated with NIDDM is thought to be primary, with a strong genetic basis, and partially irreversible. Patients with NIDDM are unable to increase their glucose oxidation normally in response to insulin to meet the energy demands of the body. Increased oxidation of lipids represents a compensatory phenomenon to meet these demands. Therapeutic use of the glucose-FFA cycle to lower blood glucose levels has yielded conflicting results. Studies are in progress to develop agents that inhibit gluconeogenesis by interfering with FFA oxidation. Nicotinic acid derivatives seem to enhance glycogen synthesis acutely by activating glycogen synthetase. Whether these or similar agents can be used to restore impaired glycogen synthesis, the most characteristic genetic defect in NIDDM, cannot be answered until the effect has been proven in chronic studies. The existence of substrate competition between amino acids and glucose, and an intrinsic hypoaminoacidaemic property of amino acids, makes it possible to expand the Randel cycle into a glucose-FFA-amino acid cycle, which integrates control of substrate disposition at the whole body level.
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PMID:Insulin action and substrate competition. 830 11

Plasma nonesterified fatty acid (NEFA) levels are increased in the insulin-stimulated state in non-insulin-dependent diabetes mellitus (NIDDM) and may contribute to the decrease in peripheral and hepatic insulin sensitivity. To test this hypothesis and to avoid the confounding effect of obesity, we examined the effect of decreasing plasma NEFA levels on peripheral and total glucose metabolism in eight non-obese, NIDDM patients. Each received 250 mg Acipimox (a nicotinic acid analogue) or placebo at 0 and 120 minutes on separate occasions. [6,6-2H2]-glucose (0 to 300 minutes) and insulin (120 to 300 minutes) were infused in each study, and isoglycemia was maintained. Plasma NEFA levels (140 +/- 30 v 600 +/- 70 mumol/L [SEM]; P < .001) and forearm NEFA uptake measured with [1-14C]-palmitate (+93 +/- 21 v +313 +/- 42 nmol x 100 mL forearm-1; P < .001) were decreased with acipimox during the basal period (90 to 120 minutes), with no change in forearm glucose uptake (+334 +/- 80 and +330 +/- 60 nmol x 100 mL forearm-1 x min-1) and hepatic glucose output ([HGO] 13.6 +/- 0.9 and 13.4 +/- 0.7 mumol.kg-1 x min-1). Serum insulin (256 +/- 12 and 266 +/- 18 pmol/L) and plasma glucose (9.5 +/- 0.6 and 9.4 +/- 0.5 mmol/L) levels were comparable during the clamp period (270 to 300 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Peripheral and hepatic insulin sensitivity in non-insulin-dependent diabetes mellitus: effect of nonesterified fatty acids. 849 15

Acanthosis nigricans is a reaction pattern to over a dozen different causes. The skin, most classic in the axilla, is dark, soft, velvet-like with fine folding and papillae. The mechanism of this skin change is decreased viscosity of extracellular matrix (ECM) combined with mechanical extrusion of ECM into papillae extending out from the upper dermis. It occurs in obesity (increased mechanical pressure on ECM), diabetes (decreased quality of glycosaminoglycans) (GAG), excess corticosteroids (decreased quality of GAG), pineal tumors (increased ECM and edema), other endocrine disorders (alterations in the quality of GAG), multiple genetic variants (structural and chemical change), from drugs such as nicotinic acid, estrogens, corticosteroids (weakened or altered GAG) and adenocarcinoma (fractions of depolymerized or altered GAG released from the tumor area are incorporated into and weaken the skin GAG). Acanthosis nigricans was first reported in 1890 as a cutaneous sign of internal malignancy. Acanthosis nigricans presents an opportunity to better understand what is occurring in the ECM in many disorders. The understanding of the association of AN and internal malignancy will expand our understanding of how a neoplasm decreases generalized ECM viscosity.
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PMID:Acanthosis nigricans--decreased extracellular matrix viscosity: cancer, obesity, diabetes, corticosteroids, somatotrophin. 850 93

Diet and drug therapy are two of the principal approaches to lipid management. The aim of both is to reduce low-density-lipoprotein (LDL) cholesterol to goal levels established by the National Cholesterol Education Program Expert Panel in its second report, based on a patient's short-term risk of a coronary event. In prescribing diet therapy, it is important to determine patients' willingness to initiate and adhere to dietary modifications, their skill at reading nutritional labels, adapting recipes, and ordering "heart-healthy" foods when eating out. Diet therapy should be directed at modifying dietary factors known to adversely influence blood cholesterol-saturated fats, cholesterol, and obesity. Diet therapy (with exercise) is not always adequate. High risk individuals with no overt coronary artery disease but with >/=2 risk factors, as well as patients with coronary artery disease, are potential candidates for drug therapy, depending on their LDL cholesterol levels. The "statins" are the drug of choice for patients with coronary disease and elevated LDL cholesterol or familial LDL-cholesterol abnormalities. These drugs increase high-density-lipoprotein (HDL) cholesterol and reduce LDL cholesterol, coronary artery disease, and total mortality. Bile acid resins lower LDL cholesterol and are often used to augment the effects of the statins and niacin. Niacin is particularly useful in the management of patients with combined hyperlipidemia and low HDL cholesterol levels. Gemfibrozil is effective in familial dysbetalipoproteinemia and is the drug of choice for patients with severely elevated serum triglycerides.
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PMID:Lipid management: current diet and drug treatment options. 890 Mar 36

GH induces lipolysis in vivo, increasing plasma free fatty acid (FFA) levels; in turn, FFA are able to reduce GH release, and acipimox, a nicotinic acid analog able to block lipolysis, enhances in normal subjects the GH response to GHRH. Obesity and old age are characterized by a blunted GH response to several stimuli, including GHRH; reports also indicate high plasma FFA levels in obesity and sometimes in the elderly. The aim of this study was to evaluate the possible role of FFA in GH release in obese and elderly subjects. According to a randomized, single blind, cross-over protocol, six healthy subjects, six obese subjects, and six elderly subjects received on 2 different days, with a 1-week interval, placebo or acipimox (250 mg, orally) at 0700 and 1100 h; GHRH [GHRH-(1-44)NH2; 50 micrograms in healthy subjects and in elderly subjects, 100 micrograms in obese subjects] was injected iv at 1300 h, and blood samples for evaluation of plasma FFA, blood glucose, serum insulin (IRI), and serum GH levels were taken from 1200 to 1500 h. Plasma FFA levels were always lower (P < 0.05) after acipimox than after placebo (0.03 +/- 0.01 vs. 0.13 +/- 0.02 g/L in healthy subjects, 0.09 +/- 0.01 vs. 0.27 +/- 0.02 g/L in obese, 0.02 +/- 0.005 vs. 0.17 +/- 0.01 g/L in elderly subjects); serum IRI levels were also lower (P < 0.05) after acipimox than after placebo in the three groups of subjects (16 +/- 3 vs. 30 +/- 5, 120 +/- 30 vs. 181 +/- 32, and 21 +/- 3 vs. 49 +/- 9 pmol/L); both FFA (P < 0.05) and IRI levels (P < 0.05) were higher in obese than in healthy or elderly subjects after placebo and acipimox. Blood glucose levels were not different in the three groups of subjects after either placebo or acipimox. The integrated GH response to GHRH-(GH delta area) was always greater (P < 0.05) after acipimox than after placebo (4677 +/- 633 vs. 1599 +/- 373 in healthy, 1469 +/- 230 vs. 343 +/- 114 in obese, 2304 +/- 759 vs. 325 +/- 133 micrograms/L.120 min in elderly subjects); after both placebo and acipimox, the GH delta area was greater (P < 0.05) in healthy subjects than in obese or elderly subjects. The GH delta area of elderly and obese subjects after acipimox was not different from the GH delta area of healthy subjects after placebo. Changes in GH delta areas were not significantly related to changes in FFA or IRI induced by acipimox; in contrast, absolute values of FFA and IRI as well as basal GH levels were all significantly related to the GH delta area. At multiple regression analysis, FFA was the only significant predictor of GH delta area. These data indicate that acute pharmacological reduction of plasma FFA levels restores the blunted GH response to GHRH commonly observed in obese and elderly subjects: however, when lipolysis is blocked to a similar extent, healthy subjects still show a higher GH delta area than obese or elderly subjects. As FFA are the best predictor of the GH delta area, we suggest that in obesity, the blunted GH release is due to high FFA levels, whereas in the elderly there might be an abnormal sensitivity to normal FFA levels.
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PMID:Restoration of growth hormone (GH) response to GH-releasing hormone in elderly and obese subjects by acute pharmacological reduction of plasma free fatty acids. 892 50


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