Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many clinical studies have shown an increased insulin response to oral glucose in patients with ischemia of the heart, lower limbs, or brain. Hyperinsulinemia also occurs in patients with angiographically proved atherosclerosis without ischemia and thus appears to be related to arterial disease and not to be a nonspecific response to tissue injury. Fasting insulin levels and insulin responses to intravenous stimuli, including glucose, tolbutamide, and arginine, are normal, suggesting a gastrointestinal factor may be involved in the increased insulin response to oral glucose. In patients with atherosclerosis, insulin sensitivity appears to be normal or enhanced with respect to both glucose and lipid metabolism. Five population studies have shown that insulin responses to glucose are higher in populations at greater risk of cardiovascular disease. Many of the hyperinsulinemic populations also had upper-body obesity, hypertriglyceridemia, lower high-density lipoprotein (HDL) levels, and hypertension. These prospective studies support an independent association between hyperinsulinemia and ischemic heart disease, although their results differ in detail. Hyperinsulinemia is associated with raised triglyceride and decreased HDL cholesterol levels. Total and low-density lipoprotein (LDL) cholesterol is less closely related to hyperinsulinemia. Upper-body adiposity is associated (in separate studies) with coronary heart disease, diabetes, hyperinsulinemia, and hypertriglyceridemia. Insulin and blood pressure are closely related in both normotensive and hypertensive people. Although obesity and diabetes are often found in hypertensive people, hyperinsulinemia also occurs in nonobese nondiabetic hypertensive people. Thus, hyperinsulinemia is closely associated with a cluster of cardiovascular risk factors, i.e., hypertriglyceridemia, low HDL levels, hypertension, hyperglycemia, and upper-body obesity. There is a possibility that insulin has a role in the sex differences in ischemic heart disease incidence and their absence in diabetes, but additional work is required for its clarification. Long-term treatment with insulin results in lipid-containing lesions and thickening of the arterial wall in experimental animals. Insulin also inhibits regression of diet-induced experimental atherosclerosis, and insulin deficiency inhibits the development of arterial lesions. Insulin stimulates lipid synthesis in arterial tissue; the effect of insulin is influenced by hemodynamic factors and may be localized to certain parts of the artery. In physiological concentrations, insulin stimulates proliferation and migration of cultured arterial smooth muscle cells but has no effort on endothelial cells cultured from large vessels. Insulin also stimulates cholesterol synthesis and LDL binding in both arterial smooth muscle cells and monocyte macrophages.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Insulin and atheroma. 20-yr perspective. 199 42

Although minimal model analysis of frequently sampled iv glucose tolerance tests (FSIGTs) to measure insulin sensitivity is well recognized, application has been limited by the need for endogenous insulin secretion. In the present study we determined whether use of exogenous insulin could permit minimal model assessment of insulin sensitivity (SI) to be extended to diabetic subjects. Normal volunteers had separate FSIGT assessments supplemented with both tolbutamide and insulin to accelerate glucose disappearance, while diabetics had a FSIGT supplemented only with insulin. There was a strong and highly significant correlation between the two assessments in normal subjects (r = 0.87; P less than 0.001), and the rank order of SI generally was maintained with the two assessments over a 3-fold range of SI; however, insulin-determined SI was 16% lower (3.4 +/- 0.4 vs. 4.1 +/- 0.4 x 10(-4) min/microU.microL; P less than 0.01). Diabetic subjects had markedly lower insulin sensitivity than controls (SI = 0.61 +/- 0.16; P less than 0.0001). Across all subjects, the level of fasting serum glucose was correlated inversely with both insulin sensitivity (r = -0.62; P less than 0.05) and acute insulin responses (r = -0.72; P less than 0.02); however, insulin sensitivity in diabetic subjects with little insulin secretion (0.6 +/- 0.2) was comparable to insulin sensitivity in diabetic subjects with near-normal responses (0.6 +/- 0.3). In subjects with fasting hyperglycemia, there were significant correlations between insulin sensitivity and body mass index, percent fat mass, and waist/hip ratio (all P less than 0.03). Among all female subjects, there was also a strong correlation between insulin sensitivity and upper body obesity, as measured by waist/hip ratio (r = -0.68; P less than 0.02). Model parameters also permitted glucose uptake to be estimated in diabetic vs. normal subjects at comparable hyperglycemia (11.1 mmol/L). Total glucose uptake was decreased in diabetic subjects (5.2 +/- 0.8 vs. 12.7 +/- 1.7 mg/min.kg in normals; P less than 0.001), insulin-dependent glucose uptake was diminished to a greater extent (1.3 +/- 0.4 vs. 6.2 +/- 1.2) than noninsulin-independent glucose uptake (3.9 +/- 0.5 vs. 6.4 +/- 0.9; both P less than 0.02). Administration of insulin permits minimal model FSIGT analysis to be applied to diabetic as well as normal subjects, yielding information about both insulin- and noninsulin-mediated glucose uptake as well as insulin sensitivity and insulin secretion.
 ...
PMID:Minimal model analysis of intravenous glucose tolerance test-derived insulin sensitivity in diabetic subjects. 222 9

In high degree obesity there a significantly smaller area under the curve of C-peptide after stimulation with Tolbutamide and significantly lower insulin sensitivity measured in vivo by euglycemic hyperinsulinemic clamp-technique (Biostator) than in moderate obesity. This allows the conclusion that high degree obesity is a risk factor for the development of diabetes mellitus.
 ...
PMID:[High-degree obesity--a risk factor for the development of diabetes mellitus]. 228 4

The authors evaluated whole blood filterability (VB) in 29 post-menopausal obese women with (n = 14) or without (n = 15) hypertension, and in 22 age matched women with normal body weight. After 3 months of a low-calorie (18 kcal/kg IBW) and moderately low-salt (max 6 g NaCl/day) diet, the obese subjects were restudied. In all women plasma fibrinogen values and various indices of metabolic status were evaluated before and after the diet and correlated to VB values. VB values and plasma fibrinogen concentrations were similar in normal controls and in women with simple obesity, whereas they were, respectively, significantly lower and higher in obese subjects with hypertension. Three months of diet significantly improved whole blood filterability and decreased fibrinogen levels in these patients. Before the diet a significant negative correlation was found between VB and plasma fibrinogen values in hypertensive obese patients. Metabolic parameters did not change in the different groups before and after the diet and did not correlate with VB values. The present study indicates that low-calorie, low-salt diet decreases plasma fibrinogen levels and improves whole blood filterability in elderly obese women with hypertension.
Acta Diabetol Lat
PMID:Effect of diet and weight loss on whole blood filterability and plasma fibrinogen values in hypertensive obese postmenopausal women. 262 50

The response of immunoreactive gastric inhibitory polypeptide (IR-GIP), immunoreactive insulin (IRI) and immunoreactive C-peptide (IR-C-peptide) to the ingestion of mixed liquid test meals containing 1031 kcal (550 ml) and 422 kcal was studied in 17 obese and 17 normal weight control subjects. When the 422 kcal load was ingested in a volume of 550 ml, the plasma IR-GIP response was significantly greater than in a volume of 225 ml at 15 and 30 min in lean and obese subjects, but the total integrated IR-GIP response was not significantly different between the obese and lean group. Also intraduodenal infusion of 150 ml (280 kcal) of the test meal elicited identical plasma IR-GIP concentrations in lean and obese subjects. An exaggerated IR-GIP response in obese subjects was seen only following the 1031 kcal load (integrated IR-GIP response: 23.6 +/- 1.9 in lean subjects vs 50.3 +/- 3.8 nmol/l/180 min in obese subjects; p less than 0.01). The IRI response was always significantly greater in obese than in lean subjects and not related to the GIP response. Fasting plasma IR-C-peptide levels were significantly elevated in obese subjects (lean: 0.52 +/- 0.04; obese: 1.42 +/- 0.12 nmol/l; p less than 0.005), but the postprandial integrated IR-C-peptide responses in the obese and lean group were identical, indicating decreased hepatic insulin extraction in obesity. It is concluded that an exaggerated IR-GIP response in obesity occurs only after ingestion of a high calorie meal probably as consequence of an increased gastric emptying rate and that the hyperinsulinemic response of obese subjects is not attributable to GIP hypersecretion.
Acta Diabetol Lat
PMID:Gastric inhibitory polypeptide (GIP) hypersecretion in obesity depends on meal size and is not related to hyperinsulinemia. 266 6

The possibility that dietary-induced thermogenesis may be decreased in obesity has been proposed in recent years. However, the results of human studies so far obtained are conflicting. The present research was undertaken in order to clarify this question. We studied postprandial thermogenesis induced by ingestion of a mixed meal and of a carbohydrate mixture in 15 normal and 12 obese subjects. Blood glucose and plasma insulin levels were measured at the same time. The data obtained have shown that the mean resting metabolic rate (RMR) expressed as a function of body weight3/4, is almost the same in obese as in normal-weight subjects (0.115 +/- 0.018 vs 0.133 +/- 0.021 kj/min/kg3/4, respectively). Moreover, the increment of mixed-meal induced thermogenesis (MM-IT) was 48 +/- 22% in normal and -0.8 +/- 12% in obese subjects, respectively (p less than 0.01). Carbohydrate induced thermogenesis (CHO-IT) appeared slightly higher in normal-weight than in obese subjects (159 +/- 66 vs 98 +/- 46). After carbohydrate ingestion we observed a higher glycemic and insulinemic response in obesity. These results indicate that thermogenesis induced by ingestion of food is reduced in obese subjects; they are also compatible with the idea that insulin resistance could play a role in this phenomenon.
Acta Diabetol Lat
PMID:Dietary-induced thermogenesis in obesity. Response to mixed and carbohydrate meals. 267 20

Patients with mild or early non-insulin-dependent diabetes mellitus often display a delay in insulin response followed by late hyperinsulinemia during oral glucose tolerance testing. Those patients with long-standing disease or elevations of fasting plasma glucose in excess of 140 mg/dl are generally hypoinsulinemic in response to an oral glucose tolerance test. Diabetic patients who do not have an acute response to intravenous glucose may have normal responses to intravenous tolbutamide or intravenous arginine, suggesting that delayed responsiveness to glucose is not due to decreased pancreatic insulin content. An association between hyperinsulinemia and hypertension has been suggested by recent studies from several laboratories. In a homogeneous population of men who suffered traumatic bilateral above-the-knee amputation in the Vietnam War with subsequent development of obesity, it was shown that there was strong correlation between hypertension and hyperinsulinemia during oral glucose tolerance testing despite only mild glucose intolerance. In addition, a subset of hypertensive women who were in their third trimester of pregnancy were markedly hyperinsulinemic during oral glucose tolerance testing in the absence of any abnormalities of glucose tolerance. Thus, the relationship between hyperinsulinemia and hypertension, and the possible reasons for this relationship, are fields of active investigation at present.
 ...
PMID:Hyperinsulinemia. 305 92

In order to establish whether obesity alters whole blood filterability, the corrected whole blood filtration (VRBC) was measured in 54 elderly obese women (mean age +/- SE = 67 +/- 2 years) without (n = 15) or with associated cardiovascular risk factors such as impaired glucose tolerance (IGT) (n = 11), non-insulin dependent diabetes mellitus (NIDDM) (n = 14) or hypertension (n = 14). Twenty-two age matched women with normal body weight participated as controls. VRBC values were similar in normal controls and obese women with normal glucose tolerance (NGT), whereas they were significantly lower in obese subjects with hypertension, NIDDM or IGT. When subjects with normal and impaired glucose tolerance were combined, a significant negative correlation was found between glucose incretory areas during OGTT and VRBC values. These data demonstrate that obesity per se does not alter whole blood filterability; furthermore, our results indicate that this modification is a precocious and sensitive index of altered glucose metabolism.
Acta Diabetol Lat
PMID:Whole blood filterability in elderly obese women. 368 12

The suggestion that insulin is associated with atherosclerosis is based on clinical, epidemiologic, and experimental evidence. In general, atherosclerosis of the coronary, cerebral, and peripheral arteries is associated with abnormally high insulin responses to oral glucose. This hyperinsulinemia is not related to acute injury or to tissue necrosis, does not occur in response to intravenous glucose or tolbutamide, and is independent of other cardiovascular risk factors. Populations who are at high risk for cardiovascular disease have higher insulin responses to oral glucose than those at lower risk. Prospective studies carried out in Australia, Finland, and France have shown that elevated insulin levels, either fasting or in response to oral glucose, have a predictive role in the development of cardiovascular disease. This association is independent of the effects of other cardiovascular risk factors. In experimental animals, insulin deficiency retards the development of diet-induced arterial disease, whereas administration of insulin promotes lesion development and prevents lesion regression. Insulin stimulates lipid synthesis in isolated arteries and stimulates proliferation and lipid accumulation in cultured arterial smooth muscle cells. The evidence linking insulin with atherosclerosis has been gathered from nondiabetic subjects; this evidence is unavailable in diabetics. As it is clear that hyperinsulinemia is often present in diabetes, either in relation to mild glucose intolerance or obesity (in noninsulin-dependent diabetes mellitus) or because of insulin therapy (in insulin-dependent diabetes mellitus), it is essential that further consideration should be given to the possibility that hyperinsulinemia may have harmful effects on the arterial wall.
 ...
PMID:Overview of the association between insulin and atherosclerosis. 390 63

Obesity is considered an insulin resistant state. Dietary guar gum supplementation is able to reduce blood glucose and plasma insulin response to a carbohydrate meal. In order to evaluate whether guar is able to reduce hyperinsulinemia and insulin resistance in gross obesity, we studied 9 obese patients, greater than 50% overweight with impaired glucose tolerance before and after 4 + 4 g/day guar for 6 weeks. Six patients repeated the treatment with 8 + 8 g/day guar after a 3-month interval. Guar was added to the usual diet in order to maintain the body weight constant. Pre-treatment and post treatment study included: total specific insulin binding on circulating monocytes; 3H-glucose infusion and euglycemic hyperinsulinemic clamp at approximately 100 microU/ml. The differences between post-treatment and pre-treatment values were not significant for any of the parameters studied. Fasting glucose production was: 2.17 +/- 0.33 SEM (pretreatment) vs 2.18 +/- 0.18 (4 + 4 g/day) vs 2.28 +/- 0.14 (8 + 8 g/day) mg/kg/min; glucose utilization was: 3.52 +/- 0.43 vs 3.22 +/- 0.44 vs 3.49 +/- 0.63 mg/kg/min; total specific insulin binding was: 2.80 +/- 0.20 vs 2.75 +/- 0.25 vs 2.78 +/- 0.31%; body weight was: 101.4 +/- 5.4 vs 100.2 +/- 6.2 vs 100.5 +/- 7.0 kg. These results indicate that dietary guar gum supplementation per se is unable to reduce insulin resistance in gross obesity if overweight is maintained constant.
Acta Diabetol Lat
PMID:Dietary guar gum supplementation does not modify insulin resistance in gross obesity. 390 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>