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

We analysed the relationship between fasting plasma glucose, carotid intima media thickness and some atherosclerosis risk factors in 307 non-diabetic individuals. Male (n = 120) and female subjects (n = 187) with a familial history of Type II diabetes mellitus and/or obesity and hyperlipoproteinaemia were examined in the age group 40-70 years. Plasma triglycerides, total and high-density-lipoprotein cholesterol, plasminogen activator inhibitor were measured by conventional methods. Specific insulin, pro-insulin and C-peptide were measured by specific enzyme immunoassay. Intima media thickness increased in quintiles for fasting plasma glucose in men, but not in women. There was a rise of triglycerides, body mass index, waist to hip ratio, plasminogen activator inhibitor, true insulin, proinsulin, C-peptide and a decrease of high-density-lipoprotein cholesterol in quintiles for fasting plasma glucose. Fasting plasma glucose was found to be significantly positively correlated to intima media thickness, body mass index, waist to hip ratio, haemoglobin A1c, insulin, C-peptide, triglycerides, plasminogen activator inhibitor and significantly negatively correlated to high density lipoprotein cholesterol. However, the correlation of fasting plasma glucose to intima media thickness was no longer significant after adjustment for age and sex. After adjustment for age and sex intima media thickness was significantly correlated to body mass index, total cholesterol, triglycerides, albuminuria and inversely correlated to high-density-lipoprotein cholesterol. In multivariate analysis age, male sex, high-density-lipoprotein cholesterol and total cholesterol were significant determinants of intima media thickness. Our data suggest that a weak association exists between fasting plasma glucose and intima media thickness, which may be mediated by a clustering of risk factors in the upper range of non-diabetic fasting plasma glucose level with a central role for dyslipidaemia.
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PMID:Relationship between fasting plasma glucose, atherosclerosis risk factors and carotid intima media thickness in non-diabetic individuals. 1033 63

The insulin resistance syndrome has been characterized by hypertension, upper body obesity, insulin resistance, hyperinsulinemia, glucose intolerance, and hypertriglyceridemia. Previous studies are inconsistent regarding the relationship between blood pressure and insulin resistance. We therefore compared the metabolic profile in 60 hypertensive subjects (mean+/-SD arterial pressure, 116+/-7 mm Hg) and 60 normotensive subjects (mean arterial pressure, 88+/-5 mm Hg) matched for age, gender, and body mass index. Hypertensives had significantly higher waist-to-hip ratio than normotensives (P=0.002). The groups did not differ in fasting plasma glucose (0.2 mmol/L, P=0.09), insulin (6 pmol/L, P=0.14), insulin sensitivity index (-0.01 micromol x kg(-1) x min(-1) x pmol/L(-1), P=0.7), and suppression of nonesterified fatty acids during a hyperglycemic clamp (1%, P=0.40). There were significant differences in fasting levels of C-peptide (50 pmol/L, P=0.004) and proinsulin (2 pmol/L, P=0.01), 2-hour postload levels of glucose (0.8 mmol/L, P=0.01) and insulin (84 pmol/L, P=0.01) after oral glucose challenge, and hepatic glucose production during the clamp (2.87 micromol x kg(-1) x min(-1), P=0.02). These differences were not significant when controlling for waist-to-hip ratio. Body mass index and waist-to-hip ratio were similarly associated with the insulin sensitivity index in the hypertensive (r=-0.59, P=0.0001 and r=-0.32, P=0.05) and normotensive (r=-0.58, P=0.0001 and r=-0.39, P=0.05) groups. Hypertension per se is not associated with insulin resistance. However, even small increments in both body mass index and waist-to-hip ratio, as often seen in hypertension, may lead to impairment in insulin sensitivity, probably mediated through altered lipid metabolism.
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PMID:Insulin resistance in hypertension is associated with body fat rather than blood pressure. 967 47

In this study involving 365 non-diabetic elderly Caucasians, we examined the relationship of immuno-specific insulin (ISI), total immuno-reactive insulin (IRI), proinsulin (PI) and proinsulin-insulin ratio (PI:ISI) to serum high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), systolic blood pressure (SBP) and diastolic blood pressure (DBP), mean blood pressure (MBP) and pulse pressure. In a multiple regression analysis, adjusted for age, sex and obesity, a 1.3-fold stronger inverse association with HDL-C levels was found for IRI than for ISI, with a 1.6-fold better fit of the regression equation. The positive association of insulin with TG was 1.6-fold stronger for IRI compared to ISI, with a 2.5-fold better fit. In contrast, the positive association of IRI with the various blood pressure parameters was 1.5-1.9-fold weaker than for ISI, with a 2.1-3.8-fold worse fit. Both PI:ISI ratio and PI were independently associated with TG levels, but not with HDL-C. The PI:ISI ratio but not PI, was associated with blood pressure, but dependent on glycaemia. In conclusion, compared to ISI, IRI overestimates the association of insulin with serum lipids and underestimates the association of insulin with blood pressure. The use of non-specific insulin assays may explain the inconsistencies in the findings of previous epidemiological studies.
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PMID:Dissimilar association of conventional immuno-reactive versus specific insulin with cardiovascular risk factors: a consequence of proinsulinaemia? 968 Dec 73

Leptin is protein produced by mature adipocytes into the system circulation and gives information to hypothalamic centers about fat amount in the organism. Leptin is supposed to play a causal role in energy output of the organism and influences the appetite (antiobese effect). Obese individuals were proved to have frequently hyperleptinemia. This disease is caused by a postreceptor disorder (however, several obese families had also normoleptinemia or even hypoleptinemia which is caused by polymorphism of Ob-gene). It was also found that leptin administration in animals leads to reduced appetite and decreased body weight. Interpretation of leptinemia in human is very complicated because leptinemia is influenced by many independent regulations (hormones, stress, food intake, motor activity atc.). Obesity is often associated with hyperinsulinemia and insulin resistance (a frequent cause of human mortality) so that correlations between insulin and leptin are intensively studied. Experimental models and animal studies revealed the existence of adipoinsular axis and it was found that insulin and leptin are contrahormones. In human studies, the majority of authors did not find correlation between leptinemia and markers of insulin secretion. Similar conclusions were drawn out in our previous paper [118]. This may be due to complex regulations of leptinemia in the organism and the use of biochemical markers with limited validity (insulin, C-peptide in fasting state and after stimulation). Therefore we decided to study correlation between leptinemia and intact proinsulin in the serum which is now considered to be the most valid marker of insulin secretion and provides information about an average "daily" insulinemia. This study was stimulated by the fact that increased leptinemia is found also in persons with prolonged hyperinsulinemia (a short-term hyperinsulinemia does not affect leptin concentration so that no available marker of insulin secretion is valid). We examined the group of 31 probands, patients of the Metabolic and Diabetologic Center at the hospital in Sternberk. They were diabetic patients of type 2 who were treated by peroral antidiabetics and insulin and who met criteria of good compensation. However, no correlation between leptinemia and proinsulinemia was found. We suppose that this failure was due to complicated fine regulations affecting leptinemia and also to the fact that intact proinsulin is not an "ideal" marker of a long-term hyperinsulinemia (correlation between insulin and leptin at euglycemic clamp indicates that there exist correlation between these parameters in human).
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PMID:[Leptin, insulin and proinsulin--their relationship]. 982 61

Low levels of sex hormone-binding globulin (SHBG) are considered to be an indirect index of hyperinsulinemia, predicting the later onset of diabetes mellitus type 2. In the insulin resistance state and in the presence of an increased pancreatic beta-cell demand (e.g. obesity) both absolute and relative increases in proinsulin secretion occur. In the present study we investigated the correlation between SHBG and pancreatic beta-cell secretion in men with different body compositions. Eighteen young men (30.0 +/- 2.4 years) with normal glucose tolerance and body mass indexes (BMI) ranging from 22.6 to 43.2 kg/m2 were submitted to an oral glucose tolerance test (75 g) and baseline and 120-min blood samples were used to determine insulin, proinsulin and C-peptide by specific immunoassays. Baseline SHBG values were significantly correlated with baseline insulin (r = -0.58, P < 0.05), proinsulin (r = -0.47, P < 0.05), C-peptide (r = -0.55, P < 0.05) and also with proinsulin at 120 min after glucose load (r = -0.58, P < 0.05). Stepwise regression analysis revealed that proinsulin values at 120 min were the strongest predictor of SHBG (r = -0.58, P < 0.05). When subjects were divided into obese (BMI > 28 kg/m2, N = 8) and nonobese (BMI < or = 25 kg/m2, N = 10) groups, significantly lower levels of SHBG were found in the obese subjects. The obese group had significantly higher baseline proinsulin, C-peptide and 120-min proinsulin and insulin levels. For the first time using a specific assay for insulin determination, a strong inverse correlation between insulinemia and SHBG levels was confirmed. The finding of a strong negative correlation between SHBG levels and pancreatic beta-cell secretion, mainly for the 120-min post-glucose load proinsulin levels, reinforces the concept that low SHBG levels are a suitable marker of increased pancreatic beta-cell demand.
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PMID:Low levels of sex hormone-binding globulin and hyperproinsulinemia as markers of increased pancreatic beta-cell demand in men. 995 50

Insulin resistance is associated not only with the classic cardiovascular risk factors of hypertension and dyslipidemia, but also with several disorders of coagulation and fibrinolysis. Elevated concentrations of the fibrinolytic inhibitor plasminogen activator inhibitor-1 are associated with insulin resistance. In experimental systems, increased expression and secretion of plasminogen activator inhibitor-1 by hepatocyte and endothelial cell lines can be induced by insulin, proinsulin-like molecules, triglyceride-rich lipoproteins and oxidized LDL, as well as by inducing insulin resistance in isolated hepatocytes. Concentrations of the endothelial cell protein von Willebrand factor are elevated in insulin-resistant states, suggesting that abnormalities of capillary endothelium, as well as those reported for endothelium-dependent vasodilatation, may play a role in the etiology of insulin resistance. Levels of a third coagulation factor, fibrinogen, are elevated in insulin-resistant subjects, an association that suggests a possible role for acute-phase cytokines in the abnormalities of coagulation and endothelial function. It is proposed that the recent observations of secretion of interleukin-6 by adipose tissue, combined with the actions of adipose tissue-expressed tumor necrosis factor-alpha in obesity-induced insulin resistance, could underlie the associations of insulin resistance with endothelial dysfunction, coagulopathy, and coronary heart disease.
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PMID:Abnormalities of coagulation and fibrinolysis in insulin resistance. Evidence for a common antecedent? 1018 59

Glucokinase (GCK) is an enzyme that regulates insulin secretion, keeping glucose levels within a narrow range. Mutations in the glucokinase gene cause a rare form of diabetes called maturity-onset diabetes of the young (MODY). An early onset (less than 25 years), autosomal dominant inheritance and low insulin secretion stimulated by glucose characterize MODY patients. Specific insulin and proinsulin were measured in serum by immunofluorimetric assays (IFMA) during a 75-g oral glucose tolerance test (OGTT). Two kindreds (SA and LZ) were studied and compared to non-diabetic unrelated individuals (control group 1) matched for age and body mass index (BMI). In one kindred, some of these subjects were also obese (BMI > 26 kg/m2), and other family members also presented with obesity and/or late-onset NIDDM. The MODY patients were also compared to a group of five of their first-degree relatives with obesity and/or late-onset NIDDM. The proinsulin profile was different in members of the two MODY kindreds. Fasting proinsulin and the proinsulin/insulin ratio were similar in MODY members of kindred LZ and subjects from control group 1, but were significantly lower than in MODY members of kindred SA (P < 0.02 and P < 0.01, for proinsulin and proinsulin/insulin ratio, respectively). Moreover, MODY members of family SA had higher levels of proinsulin and proinsulin/insulin ratio, although not significantly different, when compared to their first-degree relatives and to subjects from control group 2. In conclusion, we observed variable degrees of proinsulin levels and proinsulin/insulin ratio in MODY members of two different kindreds. The higher values of these parameters found in MODY and non-MODY members of kindered SA is probably related to the obesity and late-onset NIDDM background present in this family.
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PMID:Specific insulin and proinsulin secretion in glucokinase-deficient individuals. 1034 5

The fat gene in mice represents a recessive mutation at the carboxypeptidase E (Cpe) locus. The mutant allele (Cpe(fat)) encodes a highly unstable enzyme and produces an obesity phenotype characterized by attenuated processing of prohormones such as proinsulin that require this exopeptidase for full maturation. This article presents a preliminary physiologic and endocrinologic characterization of the stock of C57BLKS/LtJ-Cpe(fat)/Cpe(fat) mice at the backcross generation (N10) currently distributed by The Jackson Laboratory. Although previously reported not to be diabetogenic at N5, an additional five backcrosses to the C57BLKS/J background resulted in a male-biased development of both obesity and diabetes. Major differences distinguishing this mutant stock from the phenotypes produced by either the diabetes (Lepr(db)) or obese (Lep(ob)) mutations on the same inbred strain background are lack of hyperphagia and hypercorticism, sensitivity of diabetic males to exogenous insulin, and a milder and male-biased diabetes syndrome that is not associated with widespread beta-cell necrosis and islet atrophy, and that often remits with age.
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PMID:Physiologic and endocrinologic characterization of male sex-biased diabetes in C57BLKS/J mice congenic for the fat mutation at the carboxypeptidease E locus. 1040 72

Hypofibrinolysis caused by increased PAI-1 levels in patients with insulin resistance (IR) is one of the most common acquired prothrombotic states with higher risk of arterial thrombosis associated with atherosclerosis. Increased PAI-1 levels are caused by PAI-1 hyperproduction in various compartments owing to various factors (multicompartmental and multifactorial model). Metabolic compartment, including visceral adipocytes and hepatocytes, is sensitive on stimulative action of insulin, proinsulin and some cytokines. This pool is responsible for elevated PAI-1 levels in obesity. Vascular compartment, including mainly endothelium, is sensitive on thrombin, angiotensin IV, cytokines, biological active lipids and oxidative stress effect, while insulin inhibits cytokine induced PAI-1 production on contrary. This compartment is responsible for elevated PAI-1 levels in patients with type 2 diabetes mellitus and hypertension with endothelial dysfunction. PAI-1 levels in patients with IR represent cumulative production in described compartments.
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PMID:[A multicomparmental and multifactorial model of production of plasminogen activator inhibitor (PAI-1). I. Experimental studies]. 1042 16

We have studied 477 8-year-old Indian children to define the relationship between birth weight and cardiovascular risk factors, including insulin resistance syndrome (IRS) variables and plasma total and LDL cholesterol concentrations. All risk factors were strongly related to current weight. After adjustment for current weight, age, and sex, lower birth weight was associated with higher systolic blood pressure (P = 0.008), fasting plasma insulin and 32-33 split proinsulin concentrations (P = 0.08 and 0.02), glucose and insulin concentrations 30 min postglucose (P = 0.06 and 0.04), subscapular/triceps skinfold ratio (P = 0.003), and plasma total and LDL cholesterol concentrations (P = 0.002 and 0.001). Lower birth weight was associated with increased calculated insulin resistance (homeostasis model assessment [HOMA], P = 0.03), but was not related to the HOMA index of beta-cell function. The highest levels of IRS variables and total and LDL cholesterol were in children of low birth weight but high fat mass at 8 years. Taller height at 8 years predicted higher fasting plasma insulin concentrations, insulin resistance, and plasma total and LDL cholesterol concentrations. The most insulin-resistant children were those who had short parents but had themselves grown tall. Although the implications of our findings in relation to height are unclear, interventions to improve fetal growth and to control obesity in childhood are likely to be important factors in the prevention of cardiovascular disease and IRS in India.
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PMID:Insulin resistance syndrome in 8-year-old Indian children: small at birth, big at 8 years, or both? 1058 Apr 32


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