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 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A high intake of fat may increase the risk of obesity. Obesity, especially abdominal obesity, is an important determinant of the risk of developing insulin resistance and non-insulin-dependent diabetes mellitus. It is suggested that a high proportion of fat in the diet is associated with impaired insulin sensitivity and an increased risk of developing diabetes, independent of obesity and body fat localization, and that this risk may be influenced by the type of fatty acids in the diet. Cross-sectional studies show significant relationships between the serum lipid fatty acid composition, which at least partly mirrors the quality of the fatty acids in the diet, and insulin sensitivity. Insulin resistance, and disorders characterized by insulin resistance, are associated with a specific fatty acid pattern of the serum lipids with increased proportions of palmitic (16:0) and palmitoleic acids (16:1 n-7) and reduced levels of linoleic acid (18:2 n-6). The metabolism of linoleic acid seems to be disturbed with increased proportions of dihomo-gamma linolenic acid (20:3 n-6) and a reduced activity of the delta 5 desaturase, while the activities of the delta 9 and delta 6 desaturases appear to be increased. The skeletal muscle is the main determinant of insulin sensitivity. Several studies have shown that the fatty acid composition of the phosholipids of the skeletal muscle cell membranes is closely related to insulin sensitivity. An increased saturation of the membrane fatty acids and a reduced activity of delta 5 desaturase have been associated with insulin resistance. There are several possible mechanisms which could explain this relationship. The fatty acid composition of the lipids in serum and muscle is influenced by diet, but also by the degree of physical activity, genetic disposition, and possibly fetal undernutrition. However, controlled dietary intervention studies in humans investigating the effects of different types of fatty acids on insulin sensitivity have so far been negative.
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PMID:Dietary fat and insulin action in humans. 1088 98

To determine whether fasting glucose/insulin (FG/I) ratio and insulin levels 2 h after 75-g oral load of glucose (IL-2 h PG) are predictors for type 2 diabetes mellitus, a comparative 2 year follow-up study was conducted. Ninety-six healthy subjects 30 years of age or older, randomly selected from the general population of Durango, Mexico were included in two groups: 1) risk group: members had both baseline FG/I ratio and IL 2-h PG within the lower and upper quartile, respectively, and 2) control group, whose members had baseline FG/I ratio and IL 2-h PG within the second and third quartiles, respectively. Multivariate logistic regression was used to compute the relative risk for the development of type 2 diabetes. The family history of diabetes (RR 10.1; IC95% 2.7-15.8, p < 0.01), glucose intolerance (RR 9.8; IC95% 1.7-13.4, p < 0.01), abdominal obesity (RR 6.1; IC95% 1.5-10.1, p < 0.01), and the low FG/I ratio and high IL 2-h PG (RR 3.3; IC95% 1.4-8.2, p < 0.05) were strong predictors for type 2 diabetes. Critical values for predicting criteria of FG/I ratio and IL 2-h PG were of 4.0 y 180 microUI/ml, respectively. In conclusion, the measurement of FG/I ratio and IL 2-h PG is an accurate indicator for estimating the risk of developing type 2 diabetes.
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PMID:[Fasting glucose/insulin index and insulin levels 2-h after glucose load are predictors of the development of type 2 diabetes]. 1089 48

Intra-abdominal obesity is associated with cardiovascular disease and non-insulin-dependent diabetes mellitus, and physical training has been suggested to alleviate these conditions. We compared epinephrine-stimulated lipolysis in vivo in three intra-abdominal adipose tissues (ATs: retroperitoneal, parametrial, and mesenteric) and in subcutaneous AT, and we also studied the effect of physical training. Moreover, we studied the effect of physical training on epinephrine-stimulated lipolysis in muscle in vivo. Female rats were either swim trained (15 wk, n = 8) or sedentary (n = 7). Under anesthesia, a two-stage intravenous epinephrine infusion (60 min of 80 and 200 ng. kg(-1). min(-1), respectively) was carried out, and local interstitial glycerol concentration was measured by the microdialysis technique. Blood flow was measured by microspheres. Training increased blood flow in all ATs [on average: 73 +/- 12 (trained) vs. 14 +/- 4 (sedentary) ml. 100 g(-1). min(-1), P < 0. 05]; nevertheless, epinephrine-stimulated interstitial glycerol concentrations were increased or unchanged. Interstitial glycerol concentration was higher in intra-abdominal than in subcutaneous AT in both trained and sedentary rats. In skeletal muscle, interstitial glycerol concentration and blood flow did not differ between trained and sedentary rats. In conclusion, in vivo lipolysis is higher both in the basal state and during epinephrine-stimulation in intra-abdominal than in subcutaneous AT, and training may be beneficial in alleviating intra-abdominal obesity by enhancing lipolysis in intra-abdominal fat depots.
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PMID:Effect of exercise training on in vivo lipolysis in intra-abdominal adipose tissue in rats. 1095 Aug 26

The Otsuka Long-Evans Tokushima fatty (OLETF) rat is an animal model of type 2 diabetes, characterized by abdominal obesity, insulin resistance, hypertension, and dyslipidemia. To elucidate the underlying molecular mechanism of obesity and its related complications, we used representational difference analysis and identified the genes more abundantly and specifically expressed in the visceral adipose tissue (VAT) of obese OLETF rats compared with the diabetes-resistant counterpart, that is, Long-Evans Tokushima Otsuka (LETO) rats. By Northern blot analysis, we confirmed the differential expression of 13 genes, including 3 novel genes. The upregulated expression of well-characterized lipid metabolic enzymes, such as lipoprotein lipase, phosphoenolpyruvate carboxykinase, and cholesterol esterase, were observed in VAT of OLETF rats. We demonstrated the differential expression of secreted proteins in VAT of OLETF rats, such as thrombospondin 1 and contrapsin-like protease inhibitor. In contrast to lipid enzymes, the secreted proteins revealed exclusive mRNA expression and they were not detected in VAT of LETO rats. Furthermore, the novel genes OL-16 and OL-64 were also expressed specifically in VAT of OLETF rats and were absent in that of LETO rats and other tissues, including subdermal and brown adipose tissues. The C-terminal partial amino acid sequence of OL-64 revealed that it showed approximately 40% homology with alpha(1)-antitrypsin and it seemed to be a new member of the serine proteinase inhibitor (SERPIN) gene family. VAT of OLEFT rats had a unique gene expression profile, and the accumulated VAT-specific known and novel secreted proteins may play a role(s) in the pathogenesis of obesity and its related complications.
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PMID:Identification of genes specifically expressed in the accumulated visceral adipose tissue of OLETF rats. 1101 3

New-onset diabetes mellitus, clinically similar to type 2 diabetes, will affect a small proportion (1%-6%) of patients infected with human immunodeficiency virus (HIV) who are treated with HIV-1 protease inhibitors (PIs). However, insulin resistance and impaired glucose tolerance will develop during PI treatment in a considerable proportion of patients. Dyslipidemia, abdominal obesity, and loss of peripheral fat frequently coexist with insulin resistance, but it is not clear whether all of these result from a common pathogenic mechanism. Recent data suggest that insulin resistance may also be associated with HIV infection in patients not receiving PI therapy. The long-term consequences of insulin resistance in this population are not known. The effect of switching to other antiretroviral therapies has not been fully determined. Treatment of established diabetes mellitus should generally follow existing guidelines. There is no clinically useful screening test that will determine the existence and degree of insulin resistance in individual patients. It is therefore reasonable to recommend general measures to increase insulin sensitivity in all patients infected with HIV, such as weight reduction for obese persons and regular aerobic exercise.
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PMID:Disorders of glucose metabolism in patients infected with human immunodeficiency virus. 1109 14

Type 2 diabetes is a heterogeneous condition that is not attributable to a single pathophysiological mechanism. In general, both insulin resistance and impaired insulin secretion are required for the disease to become manifest. Thus, as long as the pancreatic beta cells can compensate for the degree of insulin resistance, glucose tolerance remains normal. Clustering of type 2 diabetes in certain families and ethnic populations points to a strong genetic background for the disease. However, environmental factors such as obesity and a sedentary lifestyle are usually required to unmask the genes. Impaired insulin-stimulated glucose metabolism (particularly non-oxidative) in skeletal muscle represents a key feature of type 2 diabetes and is observed early in the pre-diabetic state. It is not clear, though, whether this represents an inherited defect in muscle or whether it develops secondarily, for example, to abdominal obesity. In favour of the latter hypothesis are findings that abdominal obesity and a low metabolic rate seem to precede the development of insulin resistance in offspring of type 2 diabetic patients. According to the thrifty gene hypothesis, individuals living in an environment with an unstable food supply could increase their probability of survival if they could maximize storage of surplus energy, for instance, as abdominal fat. Exposing this energy-storing genotype to the abundance of food typical of westernized societies is detrimental, causing insulin resistance and, subsequently, type 2 diabetes. There are a number of potential thrifty genes, including those that regulate lipolysis or code for the beta3-adrenergic receptor, the hormone-sensitive lipase, and lipoprotein lipase. Type 2 diabetes develops as a consequence of a collision between thrifty genes and a hostile affluent environment. Insulin resistance is a key trigger for the disease, and optimal management of type 2 diabetes should therefore aim to ameliorate insulin resistance early.
Diabetes Obes Metab 1999 May
PMID:Insulin resistance: the fundamental trigger of type 2 diabetes. 1122 Feb 83

In Switzerland, 6% of men and 5% of women are obese (BMI > 30); 33% of men and 17% of women are overweight (BMI 25-30). Both genetic and environmental factors are responsible for obesity. There is an increased risk of C-V disease, diabetes and steato-hepatitis in abdominal obesity (abdominal circumference > 102 cm for men and > 88 cm for women). There is also an increased level of cortisol, which could be due to a difficulty to cope with psycho-social stress. Leptine and different hormones play a role in fat storage. Menopause and pregnancy are moderate risk factors for obesity. Weight gain may also result from different drugs, smoking cessation and stress. Eating disorders such as boulimia and binge eating must be diagnosed and treated. Beneficial health effect of weight loss is analysed.
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PMID:[Ten questions on the causes and consequences of obesity: stress hormones]. 1123 10

Insulin resistance can be linked to diabetes, hypertension, dyslipidemia, cardiovascular disease and other abnormalities. These abnormalities constitute the insulin resistance syndrome. Because resistance usually develops long before these diseases appear, identifying and treating insulin-resistant patients has potentially great preventive value. Insulin resistance should be suspected in patients with a history of diabetes in first-degree relatives; patients with a personal history of gestational diabetes, polycystic ovary syndrome or impaired glucose tolerance; and obese patients, particularly those with abdominal obesity. Present treatment consists of sensible lifestyle changes, including weight loss to attain healthy body weight, 30 minutes of accumulated moderate-intensity physical activity per day and increased dietary fiber intake. Pharmacotherapy is not currently recommended for patients with isolated insulin resistance.
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PMID:Insulin resistance syndrome. 1127 52

This study investigated the relationship of plasma leptin to obesity, diabetes and hyperlipidaemia in Asian Northern Indian subjects, considered to have a predisposition to abdominal obesity and metabolic syndrome. A total of 72 subjects, subcategorised into lean and obese healthy subjects, lean and obese Type 2 diabetic and lean and obese non-diabetic hyperlipidaemic subjects were recruited. High leptin values were observed in all obese groups, and obese diabetic patients showed the highest levels. In lean and obese diabetic subjects, plasma leptin did not show any correlation to any index of glycaemia. When all lean and all obese subjects were analysed in two separate groups, body mass index (BMI), percent total body fat, and body density significantly correlated with the plasma leptin levels (p<0.05). Leptin values, when correlated to all variables in all patients taken together, showed the greatest magnitude of correlation with BMI (r=0.64), percent total body fat (r=0.67), and waist circumference (r=0.51). Strong inverse correlation was seen with body density (r=-0.67). Levels of serum insulin did not show any correlation with leptin levels in all subjects combined, and separately in various groups. Multiple linear regression analysis performed in obese, non-diabetic and normolipidaemic subjects, all Type 2 diabetic and all non-diabetic hyperlipidaemic subjects separately showed that percent total body fat is the only significant predictor of plasma leptin concentration in all the 3 groups. The present study suggests that plasma leptin has a strong positive correlation with percent total body fat in Asian Northern Indian subjects. Among other components of metabolic syndrome, only abdominal obesity is weakly correlated to serum leptin levels.
Diabetes Nutr Metab 2001 Feb
PMID:Relation between plasma leptin and anthropometric and metabolic covariates in lean and obese diabetic and hyperlipidaemic Asian Northern Indian subjects. 1134 62

In many patients with human immunodeficiency virus (HIV) treated with HIV protease inhibitors, a complication develops that resembles abdominal obesity syndrome, with insulin resistance and glucose intolerance that, in some cases, progresses to diabetes. In this study, we tested the hypothesis that indinavir, an HIV-protease inhibitor, directly induces insulin resistance of glucose transport in skeletal muscle. Rat epitrochlearis muscles were incubated with a maximally effective insulin concentration (12 nmol/l) and 0, 1, 5, 20, or 40 micromol/l indinavir for 4 h. In control muscles, insulin increased 3-O-[(3)H]methyl-D-glucose (3MG) transport from 0.15 +/- 0.03 to 1.10 +/- 0.05 micromol. ml(-)(1). 10 min(-)(1). Incubation of muscles with 5 micromol/l indinavir reduced the insulin-stimulated increase in 3MG transport by 40%, whereas 20 micromol/l indinavir reduced the insulin-stimulated increase in 3MG transport by 58%. Indinavir induced a similar reduction in maximally insulin-stimulated 3MG transport in the soleus muscle. The increase in glucose transport activity induced by stimulating epitrochlearis muscles to contract was also markedly reduced by indinavir. The insulin-stimulated increase in cell-surface GLUT4, assessed using the 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis-[2-(3)H] (D-mannose-4-yloxy)-2-propylamine exofacial photolabeling technique, was reduced by approximately 70% in the presence of 20 micromol/l indinavir. Insulin stimulation of phosphatidylinositol 3-kinase activity and phosphorylation of protein kinase B were not decreased by indinavir. These results provide evidence that indinavir inhibits the translocation or intrinsic activity of GLUT4 rather than insulin signaling.
Diabetes 2001 Jun
PMID:The HIV protease inhibitor indinavir decreases insulin- and contraction-stimulated glucose transport in skeletal muscle. 1137 41


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