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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity has now developed into a world-wide epidemic and is associated with large economic costs and prevalent diseases, particularly with central body fat distribution. Insulin resistance almost invariably occurs, and might be a major trigger for disease-generating mechanisms either directly or via generation of other disease precursors ("risk factors"). The hypothalamo-pituitary-adrenal (HPA) axis seems to be hypersensitive in abdominal obesity, a statement supported by increased responses to challenges from the adrenals to central regulatory centers. Furthermore, the feedback control by central glucocorticoid receptors, probably a secondary, functional consequence of an elevated HPA axis activity, because the receptor gene appears normal. Secretion of sex steroid and growth hormones is diminished, which might be consequence of elevated HPA axis activity. Hyperandrogenicity in women is probably of adrenal origin and another consequence of the sensitivity of the HPA axis. The endocrine abnormalities thus are periodically elevated cortisol and androgen (women) concentrations, as well as low secretions of gender-specific steroid and growth hormones. Since elevated cortisol, and low sex-steroid and growth hormone secretions, probably direct storage fat to visceral depots, the multiple endocrine abnormalities probably cause enlargement of these depots. Furthermore, these hormonal abnormalities most likely at least contribute to the creation of insulin resistance with additional effects of elevated fatty acids from central fat depots, which are sensitive to lipid mobilization agents. This chain of events indicates the central role of the hypersensitive HPA axis. Known causes of sensitization of this axis have been identified in subjects with abdominal obesity, including depression, anxiety, alcohol, and smoking. A common cause of HPA axis activation is perceived stress, with a depressive, defeatist, or "helplessness" reaction. In subjects with abdominal preponderance of body fat stores a number of psychosocial and socioeconomics handicaps have been identified, hypothetically predisposing to such reactions. In a primate model (monkeys), mild psychosocial stress is followed by identical psychological, endocrine, anthropometric, and metabolic abnormalities as in humans with abdominal preponderance of body fat stores, including early signs of diabetes and cardiovascular disease. These findings strongly support the interpretation that a stress reaction activating the HPA axis is involved also in the human syndrome. Interventions with normalization of the endocrine perturbations are followed by clear improvements of the multiple abnormalities in both clinical, experimental, cellular and molecular studies, suggesting that the pathogenesis of abdominal preponderance of body fat and its endocrine, anthropometric and metabolic abnormalities are indeed consequences of the endocrine abnormalities identified.
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PMID:Body fat distribution, insulin resistance, and metabolic diseases. 929 93

At least one-third of Americans are obese, as defined by body mass indexes corresponding to body weight > or = 120% of ideal body weight, and this figure is rising steadily. Women and nonwhites have particularly high rates of obesity. Obesity greatly increases risks for many serious and morbid conditions, including diabetes mellitus, hypertension, dyslipidemia, coronary artery disease, and some cancers. Obesity is clearly associated with increased risk for mortality, but there has been controversy regarding optimal weight with respect to mortality risk. We review the literature concerning obesity and mortality, with reference to body fat distribution and weight gain, and consider potential effects of sex, age, and race on this relation. We conclude that when appropriate adjustments are made for effects of smoking and underlying disease, optimal weights are below average in both men and women; this appears to be true throughout the adult life span. Central obesity, most commonly approximated by the waist-to-hip ratio, may be particularly detrimental, although this requires further study. Weight gain in adulthood is also associated with increased mortality. These observations support public health measures to reduce obesity and weight gain, including recent recommendations to limit weight gain in the adult years to 4.5 kg (10 lb).
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PMID:Obesity and mortality: a review of the epidemiologic data. 932 85

First degree relatives of patients with non-insulin-dependent diabetes mellitus (NIDDM) have a 40% risk of developing NIDDM during their lifetime and the risk seems to be greater if the disease is inherited from the mother than from the father. It has also become clear that metabolic abnormalities are demonstrable long before the disease becomes manifest. The prediabetic state is associated with a predisposition to abdominal obesity, insulin resistance, lipid disorders, high blood pressure, and microalbuminuria, ie, the metabolic or insulin resistance syndrome. It is, however, not yet known whether treatment of these abnormalities is able to prevent progression to manifest NIDDM.
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PMID:Characterization of the prediabetic state. 932 18

Rats fed a high-fat diet develop skeletal muscle insulin resistance. There is disagreement regarding whether a decrease in the GLUT4 isoform of the glucose transporter is responsible. We found that feeding rats a high-fat diet that reduced the responsiveness of glucose transport to insulin in skeletal muscles by approximately 25-45% in 4 weeks, had no significant effect on muscle GLUT4 content. There is also controversy regarding whether the contraction/anoxia activated pathway of glucose transport stimulation is affected by fat feeding. We found that stimulation of muscle glucose transport by either swimming, in situ contractions, or anoxia was depressed to a similar extent as insulin responsiveness in high-fat-fed rats. It has been suggested that the muscle insulin resistance caused by a high-fat diet is due to increased fat oxidation and glucose-fatty acid cycle activity. However, we found that insulin-stimulated glucose transport was reduced by approximately 40% when muscles of fat-fed rats were incubated under anoxic conditions under which fatty acid oxidation should not occur. Rats maintained on the high-fat diet up to 32 weeks developed the characteristics of the abdominal obesity syndrome, including insulin resistance, hyperinsulinemia, hyperglycemia, elevated LDL cholesterol and VLDL triglycerides, and marked visceral obesity. We conclude that 1) in rats fed a high-fat diet the muscle insulin resistance is not due to a decrease in total GLUT4 content or to increased fat oxidation, 2) fat feeding also results in resistance of muscle glucose transport to stimulation via the contraction/anoxia pathway, and 3) rats fed a high-fat diet may be a useful model of the abdominal obesity syndrome.
Diabetes 1997 Nov
PMID:Insulin resistance of muscle glucose transport in rats fed a high-fat diet: a reevaluation. 935 23

Generalised obesity is a major risk factor for cardiovascular disease, diabetes, hypertension and premature death, but abdominal or central obesity is even more closely related to these. Diabetes causes accelerated atherosclerosis and this results in peripheral vascular and ischaemic heart disease and stroke, major causes of death in diabetics in the Caribbean. Diabetics who have abdominal obesity are therefore at increased risk for these events. 485 patients attending the Diabetes Referral Clinic at the University Hospital of the West Indies, Jamaica, were evaluated for abdominal obesity based on the ratio between their waist and hip measurements. There was an increase in the numbers of diabetics with increasing age. Abdominal obesity was significantly more prevalent among females (90%) than among males (34.9%) (mean 2 = 142; p < 0.0001), and massive obesity was detected in 31.1% of females. However, the prevalence of abdominal obesity among males and females was not significantly age-related. Given the high prevalence of obesity in this clinic population, more precise studies of abdominal obesity associated morbidity in diabetics should be undertaken.
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PMID:The age-prevalence profile of abdominal obesity among patients in a diabetes referral clinic in Jamaica. 936 94

We have reported three missense mutations (G188E, P207L, and D250N) in the lipoprotein lipase (LPL) gene among French-Canadians, resulting in the absence of measurable postheparin plasma LPL activity in homozygotes. Presence of triglyceride- and cholesterol-rich VLDL, as well as cholesterol-poor HDL particles, has been shown in heterozygotes affected by partial reduction in postheparin LPL activity. However, significant heterogeneity in their plasma triglyceride levels has been found, even among individuals carrying the same LPL gene mutation, indicating that factors other than LPL deficiency could affect the phenotypic expression of hypertriglyceridemia in the heterozygous state. The aim of the present study was to examine the combined effects of abdominal fat accumulation and hyperinsulinemia on plasma triglyceride levels among heterozygous patients for familial LPL deficiency. Based on sex and BMI, 43 heterozygotes (25 women and 18 men) were matched with noncarrier control subjects. Our data indicate that heterozygotes with higher abdominal fat deposition, as defined as waist girth values above the 50th percentile, had higher plasma triglyceride levels than nonobese heterozygotes. However, an important proportion of male heterozygote subjects were hypertriglyceridemic, even in absence of abdominal obesity, suggesting that another factor(s) was involved in the modulation of hypertriglyceridemia in these subjects. Indeed, multivariate analyses revealed that fasting hyperinsulinemia was a significant correlate of hypertriglyceridemia among these heterozygotes. Results of the present study indicate that abdominal obesity and hyperinsulinemia both have deleterious effects on plasma triglyceride levels in familial LPL deficiency. It is suggested that heterozygotes with moderate obesity and/or insulin resistance may be at higher risk of coronary artery disease because of the expression of an atherogenic lipoprotein phenotype among these patients.
Diabetes 1997 Dec
PMID:Hyperinsulinemia and abdominal obesity affect the expression of hypertriglyceridemia in heterozygous familial lipoprotein lipase deficiency. 939 97

Intraabdominal adiposity and insulin resistance are risk factors for diabetes mellitus, dyslipidemia, arteriosclerosis, and mortality. Leptin, a fat-derived protein encoded by the ob gene, has been postulated to be a sensor of energy storage in adipose tissue capable of mediating a feedback signal to sites involved in the regulation of energy homeostasis. Here, we provide evidence for specific effects of leptin on fat distribution and in vivo insulin action. Leptin (LEP) or vehicle (CON) was administered by osmotic minipumps for 8 d to pair-fed adult rats. During the 8 d of the study, body weight and total fat mass decreased similarly in LEP and in CON. However, while moderate calorie restriction (CON) resulted in similar decreases in whole body (by 20%) and visceral (by 21%) fat, leptin administration led to a specific and marked decrease (by 62%) in visceral adiposity. During physiologic hyperinsulinemia (insulin clamp), leptin markedly enhanced insulin action on both inhibition of hepatic glucose production and stimulation of glucose uptake. Finally, leptin exerted complex effects on the hepatic gene expression of key metabolic enzymes and on the intrahepatic partitioning of metabolic fluxes, which are likely to represent a defense against excessive storage of energy in adipose depots. These studies demonstrate novel actions of circulating leptin in the regulation of fat distribution, insulin action, and hepatic gene expression and suggest that it may play a role in the pathophysiology of abdominal obesity and insulin resistance.
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PMID:Leptin selectively decreases visceral adiposity and enhances insulin action. 939 57

The increasing prevalence of traditional atherosclerotic risk factors have been documented in Asia but the real impact on prevalence of coronary heart disease (CHD) remains unclear. Smoking, hypertension, hypercholesterolaemia, diabetes mellitus and obesity are present in only 50% of CHD. In community studies of Chinese in Hong Kong and southern mainland-China, aging, smoking and hypercholesterolaemia were found to have a less impact on endothelial function in the Chinese compared with Caucasians in London and Sydney. As endothelial dysfunction is an early event in atherogenesis, there will be a strong need to search for newer risk factors for CHD in Asia, which may become more important in many Asian countries now in the process of modernization. Recently, heterozygous hyperhomocysteinaemia (with or without folate deficiency) was found to be an independent risk factor for arterial endothelial dysfunction, and hyperhomocysteinaemia in association with smoking was a significant risk factor for premature coronary heart disease in Hong Kong Chinese. Other newer factors which have emerged include folate deficiency, low HDL-cholesterol, insulin resistance, abdominal obesity, Methylene-tetrahydrofolate Reductase and Angiotensin Converting Enzyme gene polymorphism.
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PMID:New risk factors for coronary heart disease in Asia. 946 82

Black people in the UK, in the Caribbean, and to a lesser extent in the USA, experience coronary heart disease events at different rates than white people. Despite having higher prevalence of hypertension, cigarette smoking and diabetes, black males have significantly lower coronary heart disease rates than white males, whereas no significant differences have been detected in females. The only known risk factor differences that could account for the difference in CHD rates are higher HDL cholesterol and lower triglycerides that are seen in blacks compared with whites. Obesity and, in particular abdominal obesity, seems to determine TG and HDL cholesterol levels: black males are less centrally obese than whites, while total adiposity and central distribution of fat is more predominant in black females compared with white females. We propose that the less degree of abdominal adiposity observed in black males is related with an increased anti-lipolytic effect of insulin, which could account for low triglycerides and high HDL cholesterol levels, and consequently explain the higher protection from coronary heart disease experienced by black males compared with whites and black females.
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PMID:A review on ethnic differences in plasma triglycerides and high-density-lipoprotein cholesterol: is the lipid pattern the key factor for the low coronary heart disease rate in people of African origin? 951 68

The prevention of coronary artery disease is based on the control of several factors associated with a disease or clinical condition and suspected to play a pathogenetic role, defined as 'risk factors'. Smoking is a powerful risk factor for coronary artery disease, with risk of events increasing in relation to the number of cigarettes smoked daily. Smoking cessation is associated within 3-4 years, with a significant reduction in cardiovascular risk. Hyperlipidaemia is a powerful predictor of coronary disease with a strong, independent, continuous and graded positive association between cholesterol levels and risk of coronary events. Several large studies have shown the benefit of cholesterol reduction, and there is clear evidence of the efficacy of statins in the reduction of events in primary and secondary prevention. Hypertension is a significant, strong and independent risk factor for coronary artery disease morbidity and mortality and the reduction of events and mortality by antihypertensive treatment is well documented. Obesity is associated with an increase in all-cause mortality and cardiovascular mortality, with a particularly high risk for subjects with central obesity. Central obesity is also part of the so-called 'metabolic X syndrome' including insulin resistance, which appears to be associated with a particularly high risk of coronary artery disease. Type 1 and type 2 diabetes mellitus are associated with an increased risk of cardiovascular disease, especially in women. Several studies have shown that good metabolic control and multifactorial risk factor reduction significantly lower the coronary risk in these patients. Recent evidence is accumulating that some clotting factors (fibrinogen, factor VII, von Willebrand factor) and fibrinolytic factors (t-PA and PAI-1) are associated with an increased risk of coronary artery disease. The European Concerted Action on Thrombosis (ECAT) showed that the levels of fibrinogen, von Willebrand factor antigen, and t-PA antigen are independent predictors of subsequent coronary syndromes in patients with angina pectoris, and that low fibrinogen is associated with a low risk of events despite high cholesterol levels. Post-menopausal status is associated with increased risk of coronary artery disease, particularly when menopause is premature (before the age of 45) or abrupt (surgical). There is strong, thought not yet completely definite evidence that post-menopausal hormone replacement therapy may significantly reduce the risk of events and improve survival. Hyperhomocysteinaemia is an emerging risk factor independently associated with an increased risk of coronary artery disease, cerebral vascular disease, and peripheral vascular disease. The administration of vitamin B6, B12 or folate seems to be useful and is currently under further evaluation. Recently, attention has been focused on the correlation between coronary artery disease and genetic factors, such as ACE gene polymorphism or the gene polymorphism for the IIIa-moiety of the platelet fibrinogen receptor IIb-IIIa. In primary prevention, control of the major risk factors mainly in patients with clustered factors will substantially reduce the risk of ischaemic events. Secondary prevention of CHD is based on: aggressive behavioural advice, blood pressure reduction in hypertensives, good metabolic control of diabetes, and cholesterol reduction. Aspirin, beta-blockers, ACE inhibitors, and oral anticoagulants, may be useful in selected patients.
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PMID:Classical risk factors and emerging elements in the risk profile for coronary artery disease. 951 44


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