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

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

Limited weight loss following jejunoileal bypass in 24 diabetic persons who were still distinctly overweight five to ten months after a mean weight decrease of 78 lbs. was accompanied by a return of normal fasting glucose and insulin levels, normal insulin responses, and a decrease in glucose intolerance. The glucose disappearance rate had improved in the majority of the subjects, but only three had attained values in the normal range. Concomitants of the undue hyperglycemia and/or obesity included labile and, rarely, sustained hypertension and/or cardiomegaly. The blood pressure returned to normal but heart size did not change. Electrocardiographic abnormalities noted in about one-half of the patients persisted after the operation. Triglyceride and cholesterol levels decreased. No patients had diabetic retinopathy visible on funduscopy. Proteinuria did not change in three patients. Neuropathy consisting of absent ankle reflexes and/or decreased vibration perception noted in one-half of the subjects persisted despite the improvement in carbohydrate metabolism.
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PMID:Remissions of diabetes mellitus after weight reduction by jejunoileal bypass. 72 40

Growth hormone (HGH) response to glucose-induced hyperglycemia and insulin-induced hypoglycemia in 13 obese adults without carbohydrate intolerance and with normal thyroid function were compared with 16 normal weight subjects. HGH levels measured 30 min after placing an indwelling needle in an antecubital vein were significantly lower in obese than in the non-obese controls. HGH concentrations were inversely related to the body weight in all subjects. In the obese group a suppression of serum HGH level was lacking during glucose-induced hyperglycemia and furthermore it was recorded that HGH response to insulin was significantly less as compared with controls. These data indicate that abnormal HGH response is a characteristic in obesity with normal carbohydrate tolerance and normal thyroid function. HGH is a potent physiological stimulatory of lipolysis and it is thus tempting to speculate that an impaired HGH secretion leads to a diminished lipolysis and further deposition of excessive fat in obesity.
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PMID:Abnormal growth hormone response in obesity with normal carbohydrate tolerance and normal thyroid function. 73 10

Diabetes mellitus occurs in many animals species. However, only a few have been utilized in systematic studies designed to answer unsolved problems associated with the disorder in man such as molecular basis, pathogenesis of the vascular and neural lesions, and the roles of diet, exercise and obesity. Among the animal models available, rodents have been studied most thoroughly for a number of reasons: a) short generation time (sexually mature at about 3 mo of age, gestation time 21 days) and life-span is approximately 3 yr; b) hyperglycemia and/or obesity is known to be inherited in several species; c) environmental factors can be controlled easily in the laboratory because of small size; and d) economic considerations. The better-known rodent diabetes/obesity syndromes may be categorized as follows: 1) hyperglycemic with ketoacidosis, nonobese (Chinese hamster, South African hamster); 2) hyperglycemic with insulin hypersecretion, moderate obesity and may develop ketoacidosis (diabetic mouse (db/db), spiny mouse, sand rat); and 3) less pronounced hyperglycemia with hyperinsulinemia, insulin "resistance" and marked obesity (obese (ob/ob), yellow (Ay) and New Zealand obese (NZO) mice, and the Zucker "fatty" rat). The PBB/Ld mouse, described here in detail for the first time, is a new strain of mouse that also fits into the latter category. Members of this strain following maturity develop an obesity that is characterized by increasing cellularity of adipose tissue, increased serum immunoreactive insulin, reduced glucose tolerance, fatty liver, and hyperlipidemia. Therefore, this strain of mouse represents another model for study of adult onset obesity.
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PMID:Animal models of diabetes and obesity, including the PBB/Ld mouse. 77 Jan 97

Spontaneous hyperglycemia, hyperinsulinemia and obesity are common features for at least one period of the lifetime in some strains of mice. Both genetic and environmental factors are involved in the pathogenesis of the diabetes-like syndrome, making these strains excellent models for studies in both obesity and diabetes-like states. The metabolic peculiarities can be due to a dominant gene, as for the yellow obese, or a single recessive gene, as in the obese and the diabetes mouse; or they can be of polygenic origin, as for the KK and the NZO mouse. However, the severity of the metabolic disorder is due to the interaction of the mutant genes iwth modifiers in the bat genes themselves. Studies on the pathophysiology and biochemistry of these animals have revealed interstrain differences, different patterns of development of the metabolic disorder, and different degrees of severity of the diabetes-like syndrome. Although the primary causes of the syndrome remain unclear in some strains, an involvement of hypothalamic feeding centers has been implicated.
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PMID:Laboratory animals exhibiting obesity and diabetes syndromes. 83 44

In 150 middle-aged men prone to coronary disease, long-term data based on the Chicago Coronary Prevention Evaluation Program's diet showed that there was a favorable effect on fasting glycemia level and glucose tolerance. This diet for reducing obesity and hypercholesterolemia was low in cholesterol and saturated fat and moderate in polyunsaturated and total fat, with replacement of some fat by carbohydrate. At 2 years, decreased weight and serum cholesterol values of normoglycemic men were accompanied by a modest but significant fall in fasting and postload glycemia; at 4 years. fasting glycemia levels remained slightly below baseline. For men with suspect fasting hyperglycemia at baseline, sustained fall in weight and serum cholesterol value was associated with sizeable long-term reductions in fasting glycemia and improvement of glucose tolerance. Decrease in plasma glucose was significantly related to decrease in weight. No evidence of impairment of glucose tolerance with years-long consumption of this diet was recorded.
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PMID:Plasma glucose levels: long-term effect of diet in the Chicago Coronary Prevention Evaluation Program. 83 35

Eighteen obese inpatients with insulin resistance revealed by i.v. insulin test and expressed in various grades of hyperinsulinemia and hyperglycemia were examined for plasma lipid levels. A significant positive correlation was found to be present between the plasma triglyceride (TG) level and the insulin response to glucose load. A stepwise multiple regression analysis revealed that the insulin secretory response, the plasma cholesterol level and the relative body weight contributed to the level of plasma TG. No difference was found in the grades of insulin resistance between patients with and without elevated TG. The ratio of sum of plasma insulin values to that of blood glucose values during glucose tolerance test was markedly increased in patients with elevated TG. The patients with relatively blunted insulin response and impaired glucose tolerance curves showed only slight slight hypertriglyceridemia. Endogenous hypertriglyceridemia in obesity seems to be more closely correlated with plasma insulin level, and therefore, with insulin action rather than insulin resistance.
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PMID:Relationship between insulin secretory function and endogenous hypertriglyceridemia in obese humans with insulin resistance. 96 Jan 1

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

The development of obesity, hyperglycemia, and hyperinsulinemia, was examined in obese-hyperglycemic (ob/ob) mice, their lean littermates, and homozygous lean mice (+/+) between 17 days and 8 wk of age. By 4 wk of age ob/ob mice displayed many of the metabolic characteristics that are typical of the syndrome in adult animals, including elevated systemic insulin and glucose levels, increased body weight, obesity, reduced skeletal growth, and in vivo evidence of insulin resistance. In addition, 4-wk-old lean littermates of obese mice had greater body weights, increased per cent carcass lipid, and higher insulin levels than did +/+ mice of the same age that were raised under identical conditions. At 17 or 21 days of age ob/ob mice, defined by either (1) elevated carcass fat content when compared to littermates at time of killing or (2) by phenotypic expression of obesity at 6 wk of age, exhibited moderate hyperinsulinemia, hypoglycemia, reduced skeletal growth, and "obesity", as expressed by the Lee index. The present results indicate that altered pancreatic beta-cell function, obesity, and abnormalities of somatic growth all precede the onset of hyperglycemia and insulin "resistance" in ob/ob mice. Furthermore, the occurrence of these characteristics before 17 days of age suggests that the transition to laboratory diet is not essential for the expression of the ob mutation. The present data also support recent studies that have described a small but reliable effect of the ob gene on the metabolism of heterozygous lean mice.
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PMID:The development of obesity, hyperinsulinemia, and hyperglycemia in ob/ob mice. 99 38

Various sociological and biological parameters have been studied in a population of 420 subjects - 335 men and 85 women - living in a semi rural country and having presented a myocardial infarct. Our study shows big differences in epidemiology between men and women: 1. The age of women is on an average seven years older than men (63 years against 56). 2. The women's average rate of cholesterol oversteps men's rate by 21 mg% (291 mg % against 271). 3. The blood pressure, systolic and diastolic, is distinctly higher by women (mean 171/97) tan by men (148/98). Amid women, 63% have a S.B.P. equal to or higher than 160 mm Hg against 23% by men and 56% have a D.B.P. equal to or higher than 100 mm Hg against 21 % by men. 4. Hyperglycemia is more frequent among women; man rate: 103 mg % against 88 mg % by men; 17 % of the women have an equal to or higher rate than 110 mg % (8 % among men). 5. Obesity, expressed by a weight index, equal to or higher than 120, is found in 76 % of the women and 34 % of the men. The mean index is 123 by the women and 115 by the men. 6. Cigarette smoking is far more important by men: 65 % of the men smoke at least 15 cigarettes a day with smoke inhalation. This factor is practically not met by women. The smokers get their myocardial infarct at a significantly lower age than no smoking men and women. The women of our infarct population have thus an age, a cholesterol rate, a blood pressure and a glycemia higher than men of the same population; they are more frequently overweight but they don't smoke. Consequently, metabolic agents seem to play an essential part in coronary risk in women.
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PMID:[Epidemiology of the coronary risk in a semi-rural population of 420 patients having presented a myocardial infarct]. 108 64


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