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

Obese patients who voluntarily reduce to a normal weight may develop secondary amenorrhea. Six young women who dieted to lose from 13 to 50 pounds, including four from an obese weight, were evaluated because of absent cervical mucus ferning, hypoestrogenic vaginal smears, and failure to have withdrawal menses from a progestogen. Serum FSH values were normal in all, while four had normal serum LH and two had low serum LH levels. T4 and/or T3 uptake was normal in all. The pituitary-adrenal axis was apparently intact since baseline urinary steroids were normal as was the response to both ACTH and metyrapone. Fasting serum growth hormone was markedly elevated in two and slightly elevated in three, with the other patinet demonstrating an unusually high response to glucagon/propranolol in the 30 minute specimen. These endocrine findings are similar to those observed in patients with anorexia nervosa, but the weight loss is entirely voluntary and there was no associated psychiatric abnormality.
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PMID:Amenorrhea secondary to voluntary weight loss. 48 81

1. Heat output by suspensions of isolated rat hepatocytes was determined by using a modified batch-type microcalorimeter. 2. The ratio of O(2) uptake (determined polarographically) to heat output was used to assess the metabolic efficiency of isolated hepatocytes. 3. Cells from starved or fed rats incubated in either bicarbonate-buffered physiological saline containing gelatin, or bicarbonate-buffered physiological saline containing amino acids, serum albumin and glucose showed no significant difference with respect to the ratio of O(2) uptake to heat output. 4. For liver cells from 24h-starved rats, the addition of 10mm-dihydroxyacetone and 2.5mm-fructose significantly decreased the ratio of O(2) uptake to heat output from 1.94+/-0.05 in the controls to 1.52+/-0.04 and 1.54+/-0.01mumol/J respectively. 5. Glucagon (1mum), which slightly increased both O(2) uptake and heat output, did not significantly alter the ratio. 6. The addition of extracellular 10mm-NH(4)Cl and urease to provide an energetically wasteful cycle by ensuring hydrolysis of newly synthesized urea, lowered the ratio of O(2) uptake to heat output from 1.81+/-0.08 to 1.47+/-0.06mumol/J, indicating a reduced metabolic efficiency. 7. Metabolic efficiency in rats of different dietary regimen, age and genetically based obesity was also assessed. No differences in the ratio of O(2) uptake to heat output were found between liver cell suspensions prepared from rats maintained on colony diet and high-fat diet or sucrose-rich diet nor between animals ranging from 38 to 179 days of age. Comparison of the ratio of liver cell O(2) uptake to heat output between homozygote Zucker fa/fa obese rats and their lean littermates showed no significant difference. 8. It is concluded that the ratio of O(2) uptake to heat output for isolated hepatocytes is relatively constant unless perturbed by conditions that markedly enhance substrate cycling.
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PMID:The application of microcalorimetry to the assessment of metabolic efficiency in isolated rat hepatocytes. 48 37

Twenty-one nondiabetic subjects, their weights ranging from 56 to 165 kg, received an infusion of glucose (420 mg/min), insulin (0.77 mU/kg/min), and somatostatin (500 microgram/h) for 150 min. A steady state level of plasma insulin and glucose was attained after 90 min. Endogenous insulin secretion determined by C-peptide measurement, and glucagon secretion remained suppressed throughout the period. With similar steady state levels of plasma insulin (SSPI) maintained in all subjects, the height of the steady state plasma glucose concentration (SSPG) was considered an index of total body sensitivity to insulin-mediated glucose uptake. A positive correlation between SSPG and the degree of obesity, as determined by the body mass index (BMI), was demonstrated (r = 0.70, P less than 0.001). No correlation was found between SSPI and BMI. The fasting plasma insulin concentration correlated with BMI (r = 0.82, P less than 0.0001) and SSPG (r = 0.80, P less than 0.0001). This method provides a simple safe measure of total body insulin resistance over a wide range of obesity and is independent of endogenous insulin secretion.
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PMID:A simplified method using somatostatin to assess in vivo insulin resistance over a range of obesity. 48 47

The blood glucagon concentration (fasting and in insulin hypoglycemia) was determined by radioimmunoassay in diabetic patients, relatives of diabetic patients with a normal glucose tolerance test, patients with obesity and a group of normal weight subjects. The index of glucagon rise above the fasting level and glucagon release rate were estimated. In relatives of diabetic and obese patients the initial blood glucagon concentration did not differ from that of healthy subjects. However, during insulin hypoglycemia, glucagon secretion was significantly reduced, and in relatives of diabetic patients it also proved to be delayed. A comparison of glucagon and somatostatin changes in the above mentioned patients allows to suggest participation of the somatostatin mechanism in disorders of glucagon secretion.
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PMID:Glucagon secretion in subjects with prediabetes, diabetes mellitus and obesity. 50 63

Metabolic adaptations to cyclic patterns of food intake were studied in genetically lean and obese Zucker rats. Twenty-four lean and 24 obese rats were exposed to 12 hours of light and 12 hours of dark and allowed food ad libitum. Both groups of rats ate more during the dark period of the cycle. The obese consumed nearly twice as much food as the lean during the light period of the cycle. At 4-hour intervals, rats were killed and liver and epididymal fat pads were removed for metabolic studies. Adipose tissue from lean rats demonstrated marked changes in rates of lipogenesis during the 24-hour cycle whereas adipose tissue from obese rats maintained a relatively steady rate of lipogenesis. Glucose incorporation into the glycerol moiety of triacylglycerol was nearly 3-fold higher in adipose tissue from obese rats. Liver lipogenesis in lean and obese rats followed their food intake pattern. Liver lipogenic rate (expressed per organ) was 3- to 5-fold higher in obese than lean rats during most of the 24-hour cycle. These data support the concept that the excessive fatty acids produced in the liver of obese rats are being esterified by adipose cells. Lipolytic response to glucagon was found in adipose tissue from obese rats during the dark and light periods, but only during the dark period for lean rats. These data suggest, in comparison to lean rats, that obese rats do not enter a relative catabolic state during a 24-hour cycle. A constant anabolic state in the genetically prone individual may lead to excessive lipid deposition and obesity.
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PMID:Diurnal changes in adipose and liver tissue metabolism of lean and obese Zucker rats. 57 Oct 11

Animal models with genetic or experimentally produced (lesions of hypothalamus) obesities are numerous and unlikely to ever be reduced to a single pathophysiologic entity. However, obese animals have many similar traits in common. They are all hyperinsulinemic, an abnormality that occurs early in the development of these syndromes and appears to be of prime importance in producing most of the metabolic changes observed both in the early and late phases of the obesity syndromes. In all instances, obesity is an evolutional syndrome in which the early phase is different from the later one. The early phase is principally characterized by increased hepatic very low density lipoprotein (VLDL) output, increased adipose tissue lipogenesis and VLDL uptake, hence, increased fat accretion and fat cell size. These abnormalities are secondary to hyperinsulinemia and can be reversed toward normal by normalizing circulating insulin levels. The late phase is characterized by the continuation of the disorders of the early one plus a superimposed abnormality, the insulin resistance state, that is detectable particularly at the level of adipose and muscle tissues, and eventually brings about hyperglycemia. Insulin resistance is a multifactorial pathological condition that includes at least: (a) a decrease (more or less marked) in insulin binding to target tissues that is responsible for the decrease in tissue sensitivity to the hormone; (b) intracellular defects that are probably responsible for the decreased insulin responsiveness of target tissues. The origin of hyperinsulinemia in animal obesities is still ill-defined. Lesions of the ventromedial hypothalamus (VMH) produce rapid and lasting hyperinsulinemia. Such lesions produce, in addition, increased secretion of insulin and glucagon and changes in pancreatic insulin, glucagon, and somatostatin content in subsequently perfused pancreases. The locus responsible for these effects is not defined and may actually involve a series of interrelated loci. Whatever the latter may be, one of the routes of CNS influence upon endocrine pancreas is the vagus nerve, although a humoral factor has also been claimed. The etiology of hyperinsulinemia in genetically obese animals is unknown. Genetic inheritance could bear primarily upon some hypothalamic or other CNS sites, with secondary alterations in the endocrine pancreas function, or primarily on the islets of Langerhans with possible alteration in the respective function of the A, B, and D cells with resulting excessive insulin secretion.
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PMID:Hyperinsulinemia in obesity syndromes: its metabolic consequences and possible etiology. 72 39

The response of plasma insulin concentration to an oral glucose tolerance test (OGTT) and to the maximum stimulatory effect obtained with administration of glucose, glucagon and tolbutamide was studied in 24 siblings of diabetic children and in ten obese children. Five siblings of patients with diabetes sound to have chemical diabetes had hyperinsulinism during the OGTT. Serum insulin concentrations during the maximum stimulation of the beta cells in the children with chemical diabetes, although diminished at 15 minutes, were considered not significantly different from controls. Obese children had hyperinsulinism during the OGTT and the maximum stimulation of the beta cell. The data suggest that hyperinsulinism may precede or accompany carbohydrate intolerance in siblings of diabetic children.
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PMID:Maximum stimulation of insulin secretion in children with chemical diabetes and obesity. 94 38

Serum GIP, insulin, and glucose concentrations were determined during a standard oral glucose tolerance test in 80 individuals, 45 of whom were normal and 35 of whom had adult-onset diabetes mellitus according to USPHS criteria. As a group, the diabetics had fasting hyperglycemia (219 +/- 17 mg./dl.) and, in response to glucose, displayed a peak serum glucose of 373 +/- 23 mg./dl. and sustained hyperglycemia (315 +/- 24 mg./dl.) at 180 minutes. There were no statistically significant differences in absolute serum insulin levels between the two groups. However, insulin secretion was delayed, IRI increments were smaller, and the IRI concentrations were inappropriately low for the simultaneous serum glucose concentrations in the diabetics at every time interval tested. Mean fasting serum GIP was 335 +/- 30 pg./ml. in the diabetics as against 262 +/- 15 pg./ml. in normal individuals (p less than 0.025). After the ingestion of glucose, diabetics had significantly higher (p less than 0.001) mean serum GIP levels between five and 120 minutes. By 180 minutes, serum GIP levels remained above fasting in both groups, but the diabetics had higher than normal serum concentrations (p less than 0.05). Peak serum GIP concentrations, which occurred at 30 minutes in both groups, were 1,376 +/- 106 and 806 +/- 75 pg./ml. in the diabetics and normals, respectively (p less than 0.001). Total integrated serum GIP was also greater in diabetics than normals (140,852 +/- 14,208 vs. 64,602 +/- 8,719 pg.-min./ml.-1, p less than 0.001). The higher serum GIP concentrations observed following glucose ingestion in diabetics could not be attributed to obesity or age. We conclude that both fasting and glucose-stimulated GIP concentrations are higher than normal in obese adult-onset diabetics. The significance of this observation is uncertain. However, since our current understanding suggests the GIP may be an important enteric signal for the release of insulin in man, and because GIP has been shown to stimulate the release of immunoreactive glucagon, GIP may play a role in the pathogenesis of diabetes mellitus.
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PMID:Gastric inhibitory polypeptide (GIP) in maturity-onset diabetes mellitus. 97 1

Effects of a 24 hour fast were studied in 21 obese children aged 7 to 14 and in 8 controls. Mean blood glucose (BG) during fast dropped more in controls (0.88 to 0.54 g/l) than in obese (0.90 to 0.63 g/l) Plasma cortisol changes were similar in the 2 groups, FFA increased (p less than 0.01) in the 2 groups, but the 24 hour mean level was higher in controls (4.0 mEq/l) than in obese (2.06 mEq/l). At the end of the fast, a ketonuria was present in all obese children except 2. Serum alanine dropped similarly in obese (28 to 24 muM p. cent ml) and in controls (30 to 22 muM p. cent ml). All obese exhibited at the end of the fast a significant rise (p less than 0.01) of branched chain aminoacids, not observed in controls. Responses to glucagon (0.03 mg/kg I.M.) were studied before and after fast. At time 0, BG response was higher and more prolonged in obese in spite of hyperinsulinism. At time 24 hours, BG raised from 0.50 to 0.74 g/1 and insulin from 8 to 35 muU/ml in controls, while in obese BG raised from 0.63 to 1.06 g/l and insulin from 25 to 88 muU/ml. Concomitant hyperinsulinsim and biological criteria of hypoinsulinism demonstrated in obese children the peripheral resistance to insulin. The contrast between a normal degree of protein gluconeogenesis and a reduced rate of fat mobilization during fast may be a major biological feature of obesity in childhood.
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PMID:Effect of 24 hour fast in obese children. 100 33

The hormone-substrate milieu has been investigated in male fasted lean (C57BL/6-+/+) mice and mutant obese mice of the same strain (C57BL/6-obob). The lean mouse, in winter, mobilized insufficient fat (due to inadequate stores) to permit survival beyong 3 days and was unable to achieve any degree of conservation of vital protein stores. By contrast, in summer, the same animals survived 7 days and showed evidence of greater and more sustained fat mobilization and ketosis and the ability to conserve protein. The insulin, glucagon, and insulin/glucagon molar ratios changed in both groups in a direction consistent with conversion to a catabolic state, and hence were probably largely responsible for the mobilization of substrates and stimulation of gluconeogenesis and ketogenesis. The seasonal difference in response is unexplained. The obob mice, generally employed as a model for obesity, hyperglycemia, and hyperinsulinemia showed these features but also adapted to fasting in a fashion permitting prolonged survival during this state. In a fashion analogous to that known to occur in man, these animals developed fall in glycemia, rise in circulating fat-derived substrates, and marked protein conservation. Profound fall in insulinemia was associated with a fall in glucagonemia, the latter from normal levels. Thus the initial markedly "anabolic" insulin/glucagon molar ratio diminished, but nevertheless remained higher than at any time in the lean mice. Pancreatic contents of insulin showed markedly different changes with fasting in obob compared with lean mice. The ability of the obese mouse to adapt to prolonged fasting in a fashion largely analogous to that of man renders it a useful model for the study of metabolism in this state, with the potential of applicability of findings to man.
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PMID:Hormone-substrate responses to total fasting in lean and obese mice. 109 42


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