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Query: UMLS:C0011849 (diabetes)
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Future trends in hypertensive treatment have to rely on our past and present experience with antihypertensive drugs as well as on emerging concepts of blood pressure regulation, on which some new drugs in the "pipeline" are based. Early detection of hypertension, before organ manifestations particularly in the heart, the kidney and the vessels occur, remain mandatory since in most of the patients with mild and moderate hypertension the high blood pressure is not diagnosed at all or treated inadequately. Prevention of cardiac, vascular, renal or metabolic complications has always been better for the patient and less costly than their repair or reparation. Our present treatment goals have often not reached far enough. Normalisation of blood pressure demonstrates only surrogate efficacy of our treatment. Our ultimate goal has to be improvement of total or cerebrovascular or cardiovascular and cardiac mortality. Important steps on that road are the prevention or reparation of cardiac hypertrophy, of the increased extracellular matrix and collagen deposition, the conservation of vascular integrity including both coronary and systemic microangiopathy and macroangiopathy. For the patient this means integrated care of his associated disorders that is of coronary artery disease, diabetes mellitus, lipid disorders, overweight and the metabolic syndrome. True health efficacy (= reduction of total or cerebro- and cardiovascular mortality) has been demonstrated so far only by blood pressure reduction with diuretics (thiazides) and beta-blockers in long term studies, whereas sufficient surrogate efficacy, the lowering of blood pressure, has been demonstrated with almost all the others drugs either in mono- or in combinationtherapy. Together with ACE-inhibitors, which have demonstrated their prognostic value in patients with heart failure of different causes, thiazides (as the most representative diuretic) and betablockade can be considered first line drugs in the treatment of hypertension. Long-term mortality trials for ACE-inhibitors in hypertension are needed, however, to prove that the anticipated benefit from the heart failure megatrials can also be taken for granted for hypertensive patients without coronary artery disease as well. All other drugs should not or not yet be considered first line medication, although treatment behavior in the US and in Europe shows wide-spread use of calcium antagonists in short- and long-acting dihydropyridine type hypertensive patients. No peer reviewed journal has so far published a randomized double-blind trial with the endpoint of total or cardiovascular mortality in hypertension using calcium antagonists. A recent case control study, as well as the preliminary data from MIDAS and GLANT, for which event rates are available in abstract form, suggest that short acting calcium-antagonists of the dihydropyridine type, though controlling blood pressure well, are not reducing mortality but show a trend to increase cardiovascular events particularly when given in higher doses. In contrast the unpublished data from a Chinese megatrial with dihydropyridines (STONE) demonstrate effective blood pressure reduction and benefit in mortality in a population that differs from patients in Europe and in the USA because of the low prevalence of coronary artery disease. No randomized, double blindly acquired data on mortality as the primary end of antihypertensive treatment are yet available for verapamil, diltiazem and the new class of longer acting calciumantagonists. Only when speculating from trials with calcium antagonists in coronary artery disease e.g. the DAVIT II study, one could imagine so far that prognostic benefit may be expected from drugs that do not or very little activate the adrenergic and the renin-angiotensin-aldosterone system and the baroreceptors and reduce or at least maintain heart rate. The need for double blind, randomized trials with the different Ca-antagonists is obvious, before a further w
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PMID:[Retrospective studies and prospects of therapy for hypertension]. 858 97

Obesity is a multifactorial heterogenous condition. The location of excess fat on the body determines the risk of morbidity and mortality for significant disease. Visceral, or intraabdominal, fat is the fat depot most highly associated with illness and death from cardiocerebrovascular disease and diabetes. Visceral fat is also associated with a quartet of metabolic disturbances. Referred to as the metabolic syndrome, these abnormalities include hypertension, hyperlipidemia, hyperinsulinemia, and insulin resistance. The metabolic syndrome is also present in Cushing's syndrome, which is characterized by primary hypercortisolism as well as profound visceral adiposity and obesity. The interrelationship between hyperactivation or hypersensitivity of the stress axis and disease can be elucidated by an understanding of the effect of excess glucocorticoids upon energy storage and metabolism. The complex interactions of the stress axis upon the growth and reproductive axes, as well as upon the adipose tissue, suggest that chronic stress, whether psychological and/or physical, exerts an intense effect upon body composition, which, in turn, significantly affects the longevity and survival of the organism.
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PMID:Hypercortisolism and obesity. 859 40

Insulin resistance is part of a metabolic syndrome that also includes non-insulin-dependent diabetes mellitus, dyslipidemia, obesity, and hypertension. It has been hypothesized that insulin resistance represents the primary physiological defect underlying this syndrome. Since insulin resistance is at least partially genetically determined, we hypothesized that genes influencing insulin resistance would have pleiotropic effects on a number of other traits, including triglyceride (TG) and HDL cholesterol levels, body mass index (BMI) and body fat distribution, and blood pressure levels. To investigate this hypothesis, we analyzed data obtained from individuals in 41 families enrolled in the San Antonio Family Heart Study. Statistical methods that take advantage of the relatedness among individuals were used to differentiate between genetic and nongenetic (ie, environmental) contributions to phenotypic variation between traits. Serum levels of fasting and 2-hour insulin (measured in 767 and 743 nondiabetic family members, respectively) were used as a measure of insulin resistance. The genetic correlations were high between insulin levels (both fasting and 2-hour) and each of the following: BMI, HDL level, waist-to-hip ratio, and subscapular-to-triceps ratio, indicating that the same gene, or set of genes, influences each pair of traits. In contrast, the genetic correlations of insulin levels with systolic and diastolic blood pressures were low. We have previously shown that a single diallelic locus accounts for 31% of the phenotypic variation in 2-hour insulin levels in this population. We conducted a bivariate segregation analysis to see if the common genetic effects on insulin and these other traits could be attributable to this single locus. These results indicated a significant effect of the 2-hour insulin locus on fasting insulin levels (P = .02) and BMI (P = .05), with the "high" insulin allele associated with higher levels of fasting insulin but lower levels of BMI. There was no detectable effect of this locus on HDL level, TG level, subscapular-to-triceps ratio, or blood pressure. Overall, these results suggest that a common set of genes influencing insulin levels also influences other insulin resistance syndrome-related traits, although for the most part this pleiotropy is not attributable to the 2-hour insulin level major locus.
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PMID:Genetic analysis of the IRS. Pleiotropic effects of genes influencing insulin levels on lipoprotein and obesity measures. 862 Mar 44

NIDDM and the metabolic syndrome are characterized by a low serum, HDL cholesterol content and a high triglyceride level, whereas total and LDL cholesterol concentrations are not necessarily elevated. Variable results have been reported on cholesterol absorption, elimination, and synthesis in NIDDM, but no studies are available on subjects within the normal range of blood glucose. From serum samples collected in 1985 from 203 nondiabetic men aged 51-66 years, we examined lipids, cholesterol precursors (reflecting cholesterol synthesis), and plant sterols and cholestanol (reflecting cholesterol absorption) in relation to fasting blood glucose. The findings prompted us (in 1993) to further examine 11 men from the highest and lowest glucose thirds of 203 nondiabetic men by additional dietary, serum, and fecal analyses for absorption, elimination, and synthesis of cholesterol and insulin sensitivity. In 1985, blood glucose was significantly related to LDL apolipoprotein B (P = 0.05) but not to LDL cholesterol (P = 0.19). Significantly higher serum lathosterol and desmosterol-to-cholesterol proportions and lower plant sterol and cholestanol proportions in the highest rather than the lowest glucose thirds suggested that the subjects with high normal blood glucose had decreased absorption and enhanced synthesis of cholesterol. In 1993, men with the lowest glucose versus those with the highest glucose had a lower waist-to-hip ratio, plasma HbA1c, fasting and postload insulin and glucose values, and a higher insulin sensitivity index. In agreement with the 1985 non-cholesterol sterol data, direct analyses of cholesterol metabolism showed further higher cholesterol absorption efficiency (P = 0.03) and serum plant sterol and cholestanol proportions (P < 0.001). Despite a slightly lower dietary cholesterol intake, cholesterol synthesis (P = 0.02) and serum lathosterol (P < 0.01) and desmosterol (P < 0.01) proportions were lowest in men with the lowest glucose third. We conclude that noncholesterol sterols in serum exhibits a long-lasting correlation with blood glucose level in a nondiabetic male population. Low intestinal absorption and high synthesis of cholesterol characterize men with high normal blood glucose. Differences in cholesterol metabolism could be due to underlying insulin effects associated with obesity-like fat distribution and may thus imply novel aspects in the metabolic interrelation between insulin and cholesterol in humans.
Diabetes 1996 Jun
PMID:Associations of fasting blood glucose with cholesterol absorption and synthesis in nondiabetic middle-aged men. 863 49

Clustering of elevated triglycerides, decreased high-density lipoprotein cholesterol (HDL-C), hyperuricemia, diabetes, and hypertension has been related to insulin resistance/high insulin levels and central and/or overall obesity. The extent to which these abnormalities cluster and whether hyperinsulinemia, central adiposity, and overall obesity each independently associate with this clustering were evaluated in 14,481 US whites and African-Americans 45 to 64 years of age. With the exception of hypertension, abnormalities rarely existed in isolated form. Clustering greatly exceeded chance association (P < .001). Although this clustering was greater in relative terms (ratio of observed to expected cluster frequency) in the lean and less centrally obese, it was greater in absolute terms (observed minus expected cluster frequency as a percent of total population) in the more centrally and more generally obese. The greatest excesses were found for clusters that included both hypertriglyceridemia and low HDL-C. Multiple logistic regression models showed strong and independent graded relationships of clusters with quintiles of fasting insulin (fifth quintile odds ratio, 10 to 54, P < .001) and to a lesser degree with quintiles of the waist to hip ratio (2.2 to 5.4, P < .001 for most) and of body mass index (1.6 to 4.5, P < .05 for most). In conclusion, all abnormalities cluster in excess of that predicted by chance, with clusters showing remarkable and graded independent associations with fasting hyperinsulinemia and to a lesser extent with central and overall obesity. Thus, a metabolic syndrome occurs in both lean and obese middle-aged US adults.
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PMID:Clustering of dyslipidemia, hyperuricemia, diabetes, and hypertension and its association with fasting insulin and central and overall obesity in a general population. Atherosclerosis Risk in Communities Study Investigators. 863 43

For better comprehension of the metabolic syndrome, it is necessary to differentiate the effect of insulin on glucose metabolism on the one hand, and on other metabolic activities on the other hand. Whereas glucose utilization is affected by insulin resistance, the effect of insulin on lipid metabolism, ion and aminoacid transport does not seem to be diminished. Lipid metabolism, however, seems to play a crucial role in the induction of the vicious cycle. Increased energy and fat ingestion may be due to an increased number of galanin secreting cells in the hypothalamus. The excessive fat intake results in an increased rate of release of insulin and increased influx of triglycerides into the blood. From these triglycerides an excess of free fatty acids is released by the action of lipoprotein lipase. The increased plasma free fatty acid level then results in insulin resistance affecting glucose metabolism. Also, these free fatty acids may impair the secretion of insulin. Induction of insulin resistance results in higher glucose levels, which may cause hyperinsulinemia. Hyperinsulinemia maintains the elevation of triglycerides. When diabetes becomes overt and elevated glucose levels prevail, the hyperinsulinism acts on the metabolic pathways which are still sensitive to insulin, namely lipid metabolism, aminoacid transport and ion transport.
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PMID:Hyperinsulinemia, hyperproinsulinemia and insulin resistance in the metabolic syndrome. 864 79

Secondary hyperlipoproteinemias are found in connection with other primary organic diseases. Typical examples are those seen with diabetes mellitus, liver and kidney diseases. In addition there are changes induced by hormonal dysfunctions such as hypothyroidism, by the use of oral contraceptives or in postmenopausal women. During pregnancy there is a physiological transient increase in lipoproteins. In addition to primary organic diseases there are a number of exogenous factors such as obesity, malnutrition and alcohol abuse causing hyperlipidemia. The relation between hypertension and hyperlipidemia described as familial dyslipidemic hypertension is less well known. Obesity, hypertension, dyslipidemia, hyperuricemia and impaired glucose tolerance are the basic conditions of the metabolic syndrome. Familial combined hyperlipidemia is a genetically determined, dyslipidemic syndrome with a high prevalence among patients with coronary artery disease and stroke. As there are some links between familial combined hyperlipidemia and secondary hyperlipoproteinemias, this disease entity is discussed together in this paper. Familial combined hyperlipidemia is metabolically, genetically and by this on a molecular level closely linked to familial dyslipidemic hypertension as well as the metabolic syndrome. The exact mechanism of this disease is currently unknown.
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PMID:[Secondary disorders of lipid metabolism, metabolic syndrome and familial combined hyperlipidemia]. 865 Sep 33

A total of 359 Wanigelas from Papua New Guinea and 1041 Nauruans had urinary albumin concentrations (UAC), serum insulin, and a number of cardiovascular disease (CVD) risk factors measured during population-based surveys of non-insulin-dependent diabetes mellitus. These data were used to explore the hypothesis that microalbuminuria is closely associated with insulin resistance and the metabolic syndrome. In both Nauruans and Wanigelas, worsening glucose tolerance was associated with increasing prevalence of micro- and macroalbuminuria. Within each category of glucose tolerance, microalbuminuria was associated with general worsening of cardiovascular risk factors including lipid concentrations, blood pressure and obesity, although few of the associations were statistically significant. Correlations between UAC and markers of insulin resistance (fasting insulin, fasting insulin/glucose ratio and HOMAS%, a computer-modelled estimate of insulin sensitivity) were weak and inconsistent irrespective of glucose tolerance status. Relationships between insulin sensitivity and urinary albumin in normoglycaemic Wanigelas and Nauruans, and in diabetic Nauruans, were no longer significant after adjusting for fasting glucose and body mass index. While microalbuminuria in Nauruans and Wanigelas was associated with cardiovascular risk factors irrespective of glucose tolerance, it seems unlikely on the basis of these results that the relationship is mediated through a common association with insulin resistance.
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PMID:Microalbuminuria, cardiovascular risk factors, and insulin resistance in two populations with a high risk of type 2 diabetes mellitus. 873 26

Aging is associated with an increased incidence of hypertension, noninsulin-dependent diabetes mellitus, and coronary heart disease. Because these conditions often cluster in the same individuals, there has been speculation that a common mechanism is responsible for all of these pathological states. Both epidemiological and clinical research has shown that insulin resistance and/or hyperinsulinemia are associated with glucose intolerance, dyslipidemia (high plasma triglyceride and low high-density lipoprotein-cholesterol levels), and higher systolic and diastolic blood pressures. Therefore, insulin resistance and hyperinsulinemia have been proposed as the causal link among the elements of the cluster mentioned above, now most commonly referred to as the insulin resistance syndrome, syndrome X, or the metabolic syndrome. The elderly are more glucose intolerant and insulin-resistant, but it remains controversial whether this decrease in function is an inevitable consequence of "biological aging" or the result of what might be referred to as environmental or lifestyle variables: increased obesity, a detrimental pattern of fat distribution, or physical inactivity that usually accompany age. All of these modifiable environmental factors have also been shown to result in increases in insulin resistance and hyperinsulinemia and are risk factors for the development of the diseases of the metabolic syndrome. Recent interventional studies that have attempted to reverse these conditions in the elderly have shown improved insulin sensitivity, and glucose tolerance. Insulin secretion, on the other hand, seems to decrease with age even after adjustments for differences in adiposity, fat distribution, and physical activity. This may be responsible for the glucose intolerance in the very old even after improvements have been made in their lifestyle variables.
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PMID:The effect of age on insulin resistance and secretion: a review. 882 67

One of the characteristics of peripheral vascular disease in diabetic patients is that it occurs at the time of detection of diabetes mellitus. As one of the possible pathogenic mechanisms, in non-smokers, is the sol-called metabolic syndrome (obesity, disorders in regard to metabolism of lipids and carbohydrates and hypertension). Lipoprotein Lp(a) is the most atherogenic among lipoproteins. While data on coronary arterial disease exist, although contradictory, there is a small number of those which document the same for peripheral vascular occlusive disease in diabetics. Two patients, non-smokers, with characteristic constellation of risk factors, are described as possible models for further epidemiologic examinations.
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PMID:[The metabolic syndrome and hyper-Lp(a)-lipoproteinemia in peripheral obliterative atherosclerosis: 2 case reports]. 892 51


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