Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin resistance is a major component of non-insulin-dependent diabetes mellitus (NIDDM). While a genetic contribution is likely, as yet none of several proposed candidate genes have been incriminated in the typically obese patient with NIDDM to explain their insulin resistance. Accordingly, this review focuses on some recent advances in understanding three acquired factors contributing to insulin resistance: visceral obesity, glucotoxicity and lipotoxicity. Newer computerized tomography scans allow quantitation of fat accumulating in visceral organs including the mesentery and omentum. This visceral fat relates much more to the insulin resistance syndrome than does subcutaneous fat. Moreover, exercise, as performed by active Sumo wrestlers, is associated with low visceral fat, absent hyperglycemia and absent dyslipidemia despite massive subcutaneous obesity. It remains to be seen whether exercise programs more moderate than Sumo wrestling will also mobilize visceral fat. A new metabolic pathway has recently been described whereby hexosamines are formed by an increased flux of glucose into fat and muscle. These hexosamine products appear to explain how glucotoxicity results in insulin resistance. They act as a negative feedback system to limit further glucose transport by insulin target tissue during hyperglycemia. Lipotoxicity has previously been implicated in insulin resistance by its inhibitory effect on glucose uptake by muscle because of the Randle-fatty acid cycle. Recently the role of elevated fatty acids in producing "hepatic" resistance to insulin in NIDDM has also been documented, but the site of insulin resistance may be the fat cell rather than the hepatocyte. Therapy consists mainly of hygienic measures, including caloric restriction and exercise, which can reverse all three of these acquired forms of insulin resistance. In addition, pharmacologic measures to reduce hyperglycemia can reduce the glucotoxicity and lipotoxicity. The use of insulin-sparing antihyperglycemia drugs may be particularly useful in the insulin-resistant patient to avoid weight gain while correcting the hyperglycemia.
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PMID:Reversible insulin resistance in non-insulin-dependent diabetes mellitus. 891 80

An epidemiological study was conducted to investigate the distribution of serum insulin and the relation of environmental factors to serum insulin concentrations in an urban population. In 1992 and 1993, 75 g oral glucose tolerance tests (OGTT) were performed and serum insulin concentrations determined for 2,147 subjects aged 30 to 79, randomly selected from residents of S-city in Osaka Prefecture. The subjects had received a health examination for cardiovascular disease at the National Cardiovascular Center. Median values of area under the insulin curve (AUIC), which is an index of insulin resistance, were similar for men and women, but were higher for older than younger women. Sex and age specific estimated upper limits of AUIC were set at the 95 percentile level of AUIC for the subjects without a history of stroke or myocardial infarction, and who did not have diabetes mellitus, obesity, hypertension, or dyslipidemia. Prevalence of hyperinsulinemia in the subjects was about 10 to 16%. The sex and age specific proportion of obesity, hypertriglyceridemia, hypo-HDL-cholesterolemia, and hypertension was higher for hyperinsulinemic than normoinsulinemic subjects. Relation of AUIC to obesity, dietary intake, physical activity, alcohol consumption, cigarette smoking, and antihypertensive drug use was examined in 2,039 subjects who were diagnosed as non-diabetic by OGTT. Of the environmental factors analysed, body mass index alone correlated independently with AUIC for all sex and age specific classes. For men aged 30 to 59 the waist/hip ratio correlated independently and positively with AUIC. This indicates that control of obesity, especially of upper-body obesity or visceral type obesity, should be considered important for improvement of insulin resistance.
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PMID:[Serum insulin distribution and the relationship between environmental factors and serum insulin levels in a Japanese urban population]. 891 97

Secondary prevention of arteriosclerosis tries to inhibit progression of the atherosclerotic process. Therapeutic measures focus on modification of cardiovascular risk factors and antithrombotic treatment. Hypercholesterolemia is the main risk factor for coronary artery disease. The risk of a coronary event is correlated to the plasma cholesterol level. Lowering plasma cholesterol results in reduction of vascular morbidity and mortality. Cigarette smoking is the predominant risk factor for peripheral arterial occlusive disease (PAOD). Smoking cessation reduces progression of PAOD and lowers cardiovascular morbidity and mortality. The preventive effect of antihypertensive therapy in hypertensive patients is most pronounced for cerebrovascular events. Antihypertensive measures improve prognosis after stroke and myocardial infarction. The increased cardiovascular risk in diabetics is in part explained by hyperglycemia and hyperinsulinemia, but also depends on coexisting dyslipidemia and hypertension. Intensive treatment of elevated blood glucose levels, dyslipidemia and hypertension are important preventive measures. Aspirin is highly effective in secondary prevention of vascular events. For the coronary arteries, low-dose aspirin is well established. Whether low-dose aspirin is equally effective for reducing progression of arteriosclerosis in the cerebrovascular and in the peripheral vessels is questionable. Ticlopidine serves as an alternative to aspirin; however, neutropenia may occur, which requires supervision of the patient.
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PMID:[Secondary prevention of arteriosclerosis]. 892 4

Current dietary recommendation for cardiovascular disease risk reduction and recommended dietary allowances (RDAs) were used to develop a nutritionally complete prepackaged prepared meal plan specifically designed to reduce the risk of cardiovascular disease. In the current study we tested patient acceptance of the diet as defined by measures of quality of life. In a randomized, parallel-design, multicenter clinical trial, 77 persons with hypertension, diabetes mellitus, dyslipidemia, or a combination of two or more of these conditions were recruited and randomly assigned to either a prepared meal plan (n = 39) or a comparable self-selected diet (n = 38) for 10 wk. The prepared meal plan met both the RDAs for all essential micronutrients and the dietary recommendations of national health organizations for macronutrients, cholesterol, sodium, and fiber. The prescribed self-selected diet was matched for macronutrients. Quality of life, as measured by a battery of instruments, was the major endpoint. Individuals consuming the prepared meal plan had significant improvements in mental health (P < 0.01), general perceived health (P < 0.005), daily activities (P < 0.05), work performance (P < 0.005), affect (P < 0.01), and nutritional health perceptions (P < 0.001), and reductions in nutrition hassles based on a standardized questionnaire (P < 0.001). The self-selected-diet group had significant improvements in nutritional health perceptions (P < 0.001) and affect (P < 0.001). There were significant improvements in weight (P < 0.001), blood pressure (P < 0.001), cholesterol (P < 0.002), low-density lipoproteins (P < 0.001), glucose (P < 0.014), and glycated hemoglobin (Hb A(1c) (P < 0.004) that were comparable in both groups. In summary, this study shows that a nutritionally complete diet, whether prepackaged or self-selected, improves multiple risk factors for cardiovascular disease. The prepackaged prepared meal plan had the added benefit of a greater improvement in quality of life.
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PMID:Improved quality of life in patients with generalized cardiovascular metabolic disease on a prepared diet. 894 20

Recently, the number of diabetic patients in Japan has increased and reached 6 millions, and it was estimated that 1.5 million diabetic patients were suffering from diabetic complications of microangiopathy (neuropathy, retinopathy and nephropathy) and macroangiopathy. According to the study for the causes of death among Japanese diabetic patients during 10 years from 1981 to 1990, mean longevity of diabetic patients was shorter of 9.4 years in men and 13.5 years in women than those of non-diabetics. Forty percent of diabetic patients died from the vascular diseases (ischemic heart disease 14.6%, cerebrovascular disease 13.5% and renal disease 11.2%). The frequency of death due to ischemic heart disease was almost double in diabetic patients in comparison to non-diabetics in Japan. From the data obtained from the study of Japanese-American, more than 50% of them showed abnormal glucose tolerance and the frequency of ischemic heart disease was higher twice than that of Japanese. Diabetes has been recognized as one of the important risk factors for atherosclerosis, and so many factors, such as hyperglycemia, glycation, dyslipidemia, hyperinsulinemia, insulin resistance, hypertension and obesity in diabetes, are related to atherosclerosis. The relation of these factors will be introduced. Clinically, it is very important to make a check list of these factors and make an effort to diminish them for prevention of atherosclerosis of diabetic patients.
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PMID:[Diabetes and atherosclerosis]. 895 31

Abdominal obesity has emerged as a strong and independent predictor for non-insulin dependent diabetes mellitus (NIDDM). Adiposity located centrally in the abdominal region, and particularly visceral as opposed to subcutaneous fat, is also distinctly associated with hyperlipidemia, compared with generalized distributions of body fat. These lipoprotein abnormalities are characterized by elevated very low density lipoprotein (VLDL) and low density lipoprotein (LDL) levels, small dense LDL with elevated apolipoprotein B levels, and decreased high density lipoprotein2b (HDL2b) levels. This is the same pattern seen in both familial combined hyperlipidemia and NIDDM. The pronounced hyperinsulinemia of upper-body obesity supports the overproduction of VLDL and the increased LDL turnover. We have proposed that an increase in the size of the visceral fat depot is a precursor to the increased lipolysis and elevated free fatty acid (FFA) flux and metabolism and to subsequent overexposure of hepatic and extrahepatic tissues to FFA, which then, in part, promotes aberrations in insulin actions and dynamics. The resultant changes in glucose/insulin homeostasis, lipoprotein metabolism, and vascular events then lead to metabolic morbidities such as glucose intolerance, NIDDM, dyslipidemia, and increased risk for coronary heart disease.
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PMID:Intra-abdominal fat: is it a major factor in developing diabetes and coronary artery disease? 896 90

The insulin resistance syndrome (or syndrome X) is a cluster of symptoms (dyslipidemia, impaired glucose tolerance, overweight, hypertension) associated with a higher risk of atherosclerosis. It has been suggested that hemorheological abnormalities, often found in association with most of these symptoms, may be a part of this syndrome, and possibly play a role in the circulatory abnormalities. In 22 nondiabetic women (20-54 years) presenting a wide range of body mass index (from 20 to 48 kg/m2), insulin sensitivity was assessed with the minimal model procedure, over a 180 min intravenous glucose tolerance test with frequent sampling. The insulin sensitivity index SI (i.e. the slope of the dose-response relationship between insulin increased above baseline and glucose disposal) ranges between 0.1 and 20.1 x 10(-4) min-1/microU/ml) i.e all the range of insulin sensitivity. SI was negatively correlated with blood viscosity (r = -0.530 p < 0.02), body mass index (r = 0.563 p < 0.01) and baseline insulinemia (r = 0.489 p < 0.05). These correlations were independent of each other and were not explained by relationships between SI and fibrinogen or blood lipids. Thus, blood fluidity is correlated with insulin sensitivity when it is measured with an accurate technique, suggesting that blood hyperviscosity is a symptom of insulin resistance that might be involved in the cardiovascular risk of this syndrome.
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PMID:[Blood viscosity is correlated with insulin resistance]. 896 46

We examined the association between psychosocial stress-related variables and insulin resistance syndrome (IRS) risk-factor clustering. In 90 middle-aged male volunteers, psychosocial stress-related variables, defined as feelings of excessive tiredness and as personality and behavioral factors reflecting a stress-inducing life-style (type A behavior, hostility, and anger), were significantly correlated with the hyperinsulinemia, hyperglycemia, dyslipidemia, hypertension, increased abdominal obesity, and increased plasminogen activator inhibitor-1 (PAI-1) antigen comprising the IRS. The correlations remained significant after adjusting for body mass index (BMI), age, educational level, smoking status, alcohol consumption, and physical activity. However, the different stress-related factors reflected different risk-factor clustering profiles. Type A behavior was associated with normotension and a normal metabolic profile (canonical r = .50, chi2(36) = 59.1, P = .008). Hostility was related to elevated systolic blood pressure (SBP) and elevated triglycerides (TGs) (canonical r = .38, chi2(14) = 23.2, P = .052), whereas feelings of excessive tiredness were related to abdominal obesity, augmented glycemic responses to glucose ingestion, dyslipidemia, and increased PAI-1 antigen (canonical r = .39, chi2(24) = 36.8, P = .046). Although hostility and feelings of excessive tiredness have partly overlapping but clearly different clinical and metabolic correlates, their combination represents a full-blown IRS. Thus, even though insulin resistance is presumably to some extent genetically determined, these results suggest that considering psychosocial stress may be beneficial in understanding IRS risk-factor clustering.
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PMID:Psychosocial stress and the insulin resistance syndrome. 896 88

Hyperuricemia is often associated with obesity, hypertension and dyslipidemia, and is thought to be a risk factor for cardiovascular disease, thereby making resemblance to the insulin resistance syndrome. Our data showed a low, but significant correlation between serum uric acid concentration and the degree of insulin resistance (GIR) estimated by euglycemic hyperinsulinemic clamp method in 67 subjects with combined normal glucose tolerance and IGT(r = -0.278, p < 0.05). Plasma HDL-C and TG levels were also correlated with uric acid levels. One hundred sixty NIDDM patients who had undergone the clamp study were stratified into 5 groups according to the serum uric acid level. In the top quintile (UA : 7.8 +/- 0.8 mg/dl), BMI, male prevalence, plasma TG, HDL-C, fasting IRI, and total IRI response(0 + 60 + 120 min) during meal tolerance test were significantly higher, while age and GIR value tended to be lower without significance compared with those in the bottom quintile (UA : 3.4 +/- 0.5 mg/dl). These results, which are in agreement with the previous studies, support the notion that elevated serum uric acid is a feature of insulin resistance syndrome.
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PMID:[Hyperuricemia and insulin resistance]. 897 8

Associations of cardiovascular risk factors, including several measures of adiposity, with hyperinsulinemia were assessed in 3562 elderly (71 to 93 years of age) Japanese American men from the Honolulu Heart Program who were examined between 1991 and 1993. In addition, cardiovascular risk factors measured 25 years earlier were also examined in relation to hyperinsulinemia. Hyperinsulinemia was defined as fasting insulin > or = 95th percentile (20 microU/mL) among the subset of subjects (n = 504) who were nonobese and free of clinical diabetes and glucose intolerance. When this definition was applied to the entire population, the prevalence of hyperinsulinemia declined cross-sectionally with age (P < 0.001) from 24.2% in men aged 71 to 74 years to 16.4% in men aged 85 to 93 years. Factors having a positive and independent association with hyperinsulinemia included body mass index (BMI), triglycerides, glucose, hematocrit, use of diabetic medication, heart rate, and hypertension. The association with physical activity was negative. Triglycerides, BMI, diabetic medication, hypertension, and smoking levels measured 25 years earlier were also associated independently with hyperinsulinemia. Associations were similar in nondiabetic subjects. Three measures of adiposity (BMI, waist circumference, and subscapular skinfold thickness) were independently related to hyperinsulinemia cross-sectionally. However, associations involving a difference between the 80th and 20th percentiles in each adiposity measure appeared strongest for BMI (odds ratio (OR) = 4.5, 95% confidence interval (CI) = 3.7 to 5.6) and waist circumference (OR = 4.1, 95% CI = 3.3-5.1) and slightly weaker for subscapular skinfold thickness (OR = 2.1, 95% CI = 1.8-2.5). These findings suggest that features of an insulin resistance syndrome including dyslipidemia, glucose intolerance, hypertension, and obesity, assessed both cross-sectionally and 25 years previously, are associated independently with hyperinsulinemia in elderly Japanese American men.
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PMID:Cardiovascular risk factors and hyperinsulinemia in elderly men: the Honolulu Heart Program. 897 79


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