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Query: UMLS:C0242339 (dyslipidemia)
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Patients with diabetes mellitus are at increased risk of morbidity and mortality from macrovascular disease manifesting as coronary heart disease, cerebrovascular accidents, and peripheral vascular disease. Increased frequency of dyslipidemia, hyperglycemia, obesity, hypertension, and associated nephropathy may contribute to accelerated atherogenesis in diabetic patients. Therefore, besides intensive control of hyperglycemia, management of dyslipidemia, hypertension, and obesity should also be emphasized in diabetic patients. Those who smoke should be strongly encouraged to quit smoking. Besides attempts to achieve normal levels of plasma lipoproteins, consideration also should be given to normalization of compositional abnormalities of various lipoproteins in patients with diabetes mellitus. The therapeutic goals for cholesterol reduction should be lower in diabetic patients than nondiabetic subjects. The first step is to achieve good metabolic control of diabetes mellitus by diet, exercise, and weight reduction and, if needed, with sulfonylureas or insulin therapy. Because most of the patients with insulin-dependent diabetes mellitus achieve normal levels of plasma lipoproteins with intensive insulin therapy, lipid-lowering medications are rarely needed. In patients with non-insulin-dependent diabetes mellitus, however, dyslipidemia often persists despite good glycemic control. Lipid-lowering medications should be considered in such patients. Because nicotinic acid can cause marked deterioration in glycemic control, and bile acid-binding resins may accentuate hypertriglyceridemia, these agents are less desirable for use by diabetic patients. Inhibitors of hydroxymethylglutaryl coenzyme A reductase may be preferred in patients with elevated LDL cholesterol and mld hypertriglyceridemia. For diabetic patients with marked hypertriglyceridemia, however, fibric acid derivatives should be the drug of choice.
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PMID:Lipid-lowering therapy and macrovascular disease in diabetes mellitus. 152 29

During a transverse survey, 3 groups of men with the same weight and age were compared. Group I included 42 patients with coronary disease documented by coronarography, group 2 included 19 subjects with normal coronary angiograms, and group 3 included 27 healthy controls who had not undergone coronarography. Subjects presenting diabetes or any factor associated with secondary dyslipidemia or able to modify lipid levels were excluded from study. The following parameters were measured: total cholesterol (Chol), triglycerides (TG), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), apoprotein A1 (apoA1), apoprotein B (apoB), lipoprotein (a) or Lp(a), fibrinogen, insulinemia and plasminogen activator inhibitor activity (PAI). The levels of chol, LDL-C and ApoB were the same in the 3 groups. The levels of TG, HDL-C, apoA1 and the ApoA-1/APoB ratio were significantly different between groups 1 and 2, on the one hand, and groups 1 and 3, on the other hand. The levels of Lp(a) and insulin were similar in the 3 groups. Fibrinogen levels were slightly higher in group 1 than in group 3. There was no significant difference between groups 1 and 2 with regard to any of the parameters. Subjects with angiographically normal coronary arteries and subjects with documented coronary disease exhibited similar lipid abnormalities. In this study, TG, HDL-chol, apoA1 and the apoB ratio were better predictors of cardiovascular risk than Chol, LDL-C or apoB.
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PMID:[Lipid indicators of vascular risk. A cross-sectional study of a group of coronary patients, a group of subjects with normal coronary angiography and a control group]. 156 63

The effect of metformin treatment was studied in 13 patients with noninsulin-dependent diabetes mellitus (NIDDM), whose fasting plasma glucose concentration was greater than 10 mmol/L with maximal sulfonylurea doses. Patients were studied before and 3 months after receiving 2.5 g/day metformin. The fasting plasma glucose concentration (12.4 +/- 0.8 vs. 8.8 +/- 0.7 mmol/L), mean hourly postprandial plasma glucose concentration from 0800-1600 h (14.0 +/- 1 vs. 9.4 +/- 0.9 mmol/L), and glycosylated hemoglobin level (12.3 +/- 0.6% vs. 9.0 +/- 0.6%) were all significantly (P less than 0.005-0.001) lower after the administration of metformin. The improvement in glycemic control was associated with a 24% increase (P less than 0.05) in insulin-stimulated glucose uptake during glucose clamp studies and a 16% decrease in basal hepatic glucose production (P less than 0.05). Mean hourly concentrations of plasma insulin (411 +/- 73 vs. 364 +/- 73 pmol/L) and FFA concentrations (440 +/- 31 vs. 390 +/- 40 mumol/L) were also lower after 3 months of metformin treatment. However, neither insulin binding nor insulin internalization by isolated monocytes changed in response to metformin. Finally, plasma triglyceride, very low density lipoprotein triglyceride, and very low density lipoprotein cholesterol were significantly decreased (P less than 0.01-0.001), and high density lipoprotein cholesterol was significantly increased (P less than 0.001) after metformin treatment. Thus, the addition of metformin to sulfonylurea-treated patients with NIDDM not in good glycemic control significantly lowered fasting and postprandial plasma glucose concentrations, presumably due to the combination of enhanced glucose uptake and decreased hepatic glucose production. Since the dyslipidemia present in these patients also improved, the results suggest that metformin may be of significant clinical utility in patients with NIDDM not well controlled with sulfonylurea compounds.
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PMID:Combined metformin-sulfonylurea treatment of patients with noninsulin-dependent diabetes in fair to poor glycemic control. 156 49

As shown by large-scale clinical trials, the antihypertensive effectiveness of diuretics has been associated with a dramatic decrease in the incidence of stroke. This decrease, however, has not been accompanied by a similar reduction in atherosclerotic complications of hypertension, perhaps because other risk factors are important contributors to cardiovascular disease. In particular, a pathophysiologic relationship appears to exist between high blood pressure, left ventricular hypertrophy, diabetes and dyslipidemia. Thus, metabolically neutral antihypertensive agents such as calcium antagonists, which have no adverse effects on serum lipids and insulin sensitivity and can reduce left ventricular mass, are particularly suitable for the treatment of hypertension and attendant cardiovascular complications.
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PMID:Calcium antagonists for the treatment of systemic hypertension. 157 72

Many studies have shown that hyperinsulinemia and/or insulin resistance are related to various metabolic and physiological disorders including hypertension, dyslipidemia, and non-insulin-dependent diabetes mellitus. This syndrome has been termed Syndrome X. An important limitation of previous studies has been that they all have been cross sectional, and thus the presence of insulin resistance could be a consequence of the underlying metabolic disorders rather than its cause. We examined the relationship of fasting insulin concentration (as an indicator of insulin resistance) to the incidence of multiple metabolic abnormalities in the 8-yr follow-up of the cohort enrolled in the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease in Mexican Americans and non-Hispanic whites. In univariate analyses, fasting insulin was related to the incidence of the following conditions: hypertension, decreased high-density lipoprotein cholesterol concentration, increased triglyceride concentration, and non-insulin-dependent diabetes mellitus. Hyperinsulinemia was not related to increased low-density lipoprotein or total cholesterol concentration. In multivariate analyses, after adjustment for obesity and body fat distribution, fasting insulin continued to be significantly related to the incidence of decreased high-density lipoprotein cholesterol and increased triglyceride concentrations and to the incidence of non-insulin-dependent diabetes mellitus. Baseline insulin concentrations were higher in subjects who subsequently developed multiple metabolic disorders. These results were not attributable to differences in baseline obesity and were similar in Mexican Americans and non-Hispanic whites. These results support the existence of a metabolic syndrome and the relationship of that syndrome to multiple metabolic disorders by showing that elevations of insulin concentration precede the development of numerous metabolic disorders.
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PMID:Prospective analysis of the insulin-resistance syndrome (syndrome X). 158 98

Non-insulin-dependent diabetes (NIDDM) has long been recognized as being associated with a cluster of disorders including obesity, hypertension, dyslipidemia, and atherosclerotic heart disease. It was only recently, however, that Reaven, DeFronzo, and Ferrannini with techniques to quantitate insulin resistance suggested that this represents a common factor in this group of disorders and that hyperinsulinemia resulting from insulin resistance could be the cause of the hypertension, dyslipidemia, and atherosclerosis. The names syndrome X or the insulin-resistance syndrome have been used to identify this pathological entity, and considerable investigations have been done and are in progress to establish whether or not these coexisting disorders represent an as yet unexplained association of cardiovascular risk factors or if, indeed, insulin resistance and hyperinsulinism represent the primary cause for most of the other disorders. To paraphrase a philosophical comment, if syndrome X did not exist, we probably would have had to invent it. In addition to the intellectual satisfaction of being able to "lump" these diverse ills under a single etiology, the main value of grouping these disorders as a syndrome is to continually remind physicians that the therapeutic goals are not only to correct hyperglycemia in NIDDM but also to manage the elevated blood pressure and dyslipidemia that cause cerebrovascular and cardiac morbidity as well as mortality in these patients. Having a syndrome X reduces the fragmentation of medical care among subspecialties and decreases the likelihood of prescribing drugs that correct hypertension but raise lipids or drugs that lower lipids but raise blood glucose. Finally, it encourages the selection of drugs that reduce hyperglycemia without increasing insulin secretion and to the development of new drugs for this purpose. Unfortunately, the concept of insulin resistance with hyperinsulinism being a cause of the other associated disorders is still unproved but continues to be open to experimental investigation. The remainder of this article reviewed the use of sulfonylureas in the management of NIDDM, discussed new molecular and cellular mechanisms by which they promote insulin secretion, and reviewed the controversy as to whether an extrapancreatic action contributes to their glucose-lowering effects in NIDDM. A closing section listed some other oral drugs that can lower blood glucose without stimulating the pancreatic beta cell. Their insulin-sparing hypoglycemic effect makes them potentially useful in NIDDM therapy, particularly if the fundamental premise of syndrome X is substantiated, which implicates hyperinsulinemia as contributing to the morbidity and mortality from atherosclerotic vascular disease.
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PMID:Type II diabetes and syndrome X. Pathogenesis and glycemic management. 161 69

Recent research has demonstrated that reduced insulin-stimulated glucose metabolism in skeletal muscle (insulin resistance) and hyperinsulinism are common features in widespread diseases such as essential hypertension, android obesity, non-insulin dependent diabetes mellitus, dyslipidemia (in the form of raised serum triglyceride and reduced serum high-density lipoprotein (HDL) cholesterol) and arteriosclerosis. Simultaneously, investigations in a comprehensive group of healthy middle-aged men have revealed insulin resistance in one fourth. On the basis of these observations, a working hypothesis is suggested which postulates that genetic abnormalities in one or more of the candidate genes in the modes of action of insulin occur in a great proportion of the population. These may result in insulin resistance (primary genetic insulin resistance). Primary insulin resistance may be potentiated by a series of circumstances such as ageing, high-fat diet, lack of physical activity, hormonal and metabolic abnormalities or drugs (secondary insulin resistance). As a consequence of the reduced effect of insulin on muscle tissue, compensatory hyperinsulinism develops. Depending on the remaining vulnerability of the individual the hyperinsulinism is presumed to result in development of one or more phenotypes. For example if the beta-cells of the pancreas are unable to secrete sufficient insulin to compensate the insulin resistance on account of genetic defects, glucose intolerance will develop. In a similar manner, hyperinsulinism in insulin-resistant individuals who are predisposed to essential hypertension is presumed to reveal genetic defects in the blood pressure regulating mechanisms and thus contribute to development of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Insulin resistance--a physiopathological condition with numerous sequelae: non-insulin-dependent diabetes mellitus (NIDDM), android obesity, essential hypertension, dyslipidemia and atherosclerosis]. 163 67

Hypertension is only one component of a multifaceted metabolic-hemodynamic complex that also includes obesity, subtle and overt glucose intolerance, dyslipidemia, enhanced vascular resistance and accelerated atherosclerosis. Results of a number of studies in the past 5 years have shown that even nonobese, nondiabetic individuals with hypertension display insulin resistance, which is located in peripheral tissues (primarily skeletal muscle), is limited to nonoxidative pathways of glucose disposal, and appears to be directly correlated with the severity of hypertension. Insulin resistance and associated hyperinsulinemia in hypertensive individuals are also associated with increased plasma triglyceride levels and decreased high-density lipoprotein concentrations, which likely contributes to enhanced atherosclerosis. Hyperinsulinemia may directly promote atherosclerosis by enhancing LDL-cholesterol accumulation in vessel walls, vascular smooth muscle migration, and proliferation, augmenting connective tissue synthesis in the vascular wall, and decreasing the regression of lipid plaques. The enhanced peripheral vascular resistance that characterizes insulin resistance/hyperinsulinemic states may be related to decreased vascular smooth muscle responses to insulin, which normally modulates (attenuates) vascular contractile responses to vasoactive agents.
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PMID:Insulin resistance, hyperinsulinemia, dyslipidemia, hypertension, and accelerated atherosclerosis. 163 39

The objective of treating patients with hypertension is not simply to reduce blood pressure but rather to prevent the associated morbidity and mortality. Recent assessments of clinical trials have shown that while the risk of stroke is consistently lower with antihypertensive therapy, the same degree of success has not been demonstrated for coronary artery disease (CAD). Although there are many explanations of why we have not done as well in preventing CAD, one possibility is that the therapy used in clinical trials, primarily thiazide diuretics and beta-adrenoreceptor blockers, has increased the patient's risk of developing coronary atherosclerosis or lethal arrhythmias. Four classes of antihypertensive agents are recommended for initial therapy--thiazide diuretics, beta-adrenoreceptor blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium entry blockers. The metabolic effects of thiazide diuretics include electrolyte disturbances (hypokalemia, hypomagnesemia, and hyponatremia), dyslipidemia (increased triglycerides), abnormalities of glucose metabolism (hyperglycemia, hyperinsulinemia, and peripheral insulin resistance), and hyperuricemia. beta-Adrenoreceptor blockers have many of the same metabolic adverse reactions. beta-Adrenoreceptor blockers without intrinsic sympathomimetic activity (ISA) also cause dyslipidemias (lowered high-density lipoprotein cholesterol and increased triglycerides) and abnormalities of glucose metabolism (hyperglycemia, hyperinsulinemia, and peripheral insulin resistance). beta-Adrenoreceptor blockers with ISA and third-generation beta-blockers with selective partial agonist activity (celiprolol and dilevalol) do not cause dyslipidemia and to date do not appear to induce abnormalities in glucose metabolism. ACE inhibitors may decrease triglycerides and increase high-density lipoprotein cholesterol, and captopril may improve insulin sensitivity. Calcium entry blockers are metabolically neutral.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolic considerations in the choice of therapy for the patient with hypertension. 167 Nov 90

Epidemiological evidence supports a link between hyperinsulinemia and blood pressure. In nondiabetic, normotensive individuals, the male sex, age, obesity, and body fat distribution all are associated with higher systolic and diastolic blood pressure and with higher plasma insulin concentrations. Nevertheless, when accounting for the above physiological variables, blood pressure still is independently related to plasma insulin. In the general population, hypertensive individuals have multiple metabolic abnormalities (glucose intolerance, hyperinsulinemia, and dyslipidemia). A striking pattern of overlap exists among obesity, diabetes, and hypertension. Physiological studies (euglycemic insulin clamp) have shown that essential hypertension per se is a state of insulin resistance: lean, nondiabetic subjects with untreated hypertension have a mean 40% reduction in the ability of physiological hyperinsulinemia to stimulate whole-body glucose uptake. Other insulin actions (suppression of hepatic glucose output, lipolysis, lipid oxidation, and promotion of K+ uptake) are conspicuously preserved. In perfused forearm studies, local (intra-arterial) hyperinsulinemia induces subnormal rates of glucose uptake and glycogen synthesis in the skeletal muscle of individuals with essential hypertension. In the San Antonio Heart Study, parental history of non-insulin-dependent diabetes mellitus (NIDDM) is associated with hyperinsulinemia and higher blood pressure and serum lipid levels in nondiabetic probands. In this biethnic population, however, hyperinsulinemia and NIDDM are more prevalent (approximately threefold) among Mexican-Americans than non-Hispanic whites, but hypertension is more prevalent among the latter.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Essential hypertension: an insulin-resistant state. 169 27


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