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)

It is clearly recognized that patients with NIDDM have an increased risk for CHD. Recent data indicate that persons with glucose concentrations in the nondiabetic range also may be at higher risk for CHD. These associations may not represent cause and effect, however. Emerging data suggest that hyperglycemia and CHD may both arise from hyperinsulinemia/insulin resistance. In support of this hypothesis are studies showing that NIDDM and CHD have many risk factors in common, including age, elevated blood pressure, dyslipidemia, adiposity, and a central pattern of fat distribution. Moreover, these risk factors are frequent concomitants of hyperinsulinemia, itself a risk factor for CHD and perhaps for NIDDM. Although the duration of NIDDM has been infrequently related to risk of CHD, the authors hypothesize that duration of hyperinsulinemia/insulin resistance would be a more sensitive marker for risk of CHD. The relation of IDDM to CHD is a different situation. The etiological process leading to IDDM, namely the destruction of beta-cells in genetically predisposed persons, is not related to cardiovascular risk. However, IDDM patients still have an excess of CVD, the risk factors for which may vary according to the location of the diseases (e.g., LEAD vs. CHD). There is a strong relationship between proteinuria and CVD, which has led to a general theory of vascular complications in IDDM based on defective heparan sulfate metabolism (Steno hypothesis). Recent evidence challenges parts of this hypothesis, and the possibility is raised that a higher case-fatality rate in a subgroup of patients with both renal and CVD explains part of the renal connection, as does the general worsening of CVD risk factors.
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PMID:Diabetes mellitus and macrovascular complications. An epidemiological perspective. 139 12

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

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

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

Non-insulin-dependent (type II) diabetes mellitus is an inherited metabolic disorder characterized by hyperglycemia with resistance to ketosis. The onset is usually after age 40 years. Patients are variably symptomatic and frequently obese, hyperlipidemic and hypertensive. Clinical, pathological and biochemical evidence suggests that the disease is caused by a combined defect of insulin secretion and insulin resistance. Goals in the treatment of hyperglycemia, dyslipidemia and hypertension should be appropriate to the patient's age, the status of diabetic complications and the safety of the regimen. Nonpharmacologic management includes meal planning to achieve a suitable weight, such that carbohydrates supply 50% to 60% of the daily energy intake, with limitation of saturated fats, cholesterol and salt when indicated, and physical activity appropriate to the patient's age and cardiovascular status. Follow-up should include regular visits with the physician, access to diabetes education, self-monitoring of the blood or urine glucose level and laboratory-based measurement of the plasma levels of glucose and glycated hemoglobin. If unacceptably high plasma glucose levels (e.g., 8 mmol/L or more before meals) persist the use of orally given hypoglycemic agents (a sulfonylurea agent or metformin or both) is indicated. Temporary insulin therapy may be needed during intercurrent illness, surgery or pregnancy. Long-term insulin therapy is recommended in patients with continuing symptoms or hyperglycemia despite treatment with diet modification and orally given hypoglycemic agents. The risk of pancreatitis may be reduced by treating severe hypertriglyceridemia (fasting serum level greater than 10 mmol/L) and atherosclerotic disease through dietary and, if necessary, pharmacologic management of dyslipidemia. Antihypertensive agents are available that have fewer adverse metabolic effects than thiazides and beta-adrenergic receptor blockers. New drugs are being developed that will enhance effective insulin secretion and action and inhibit the progress of complications.
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PMID:Non-insulin-dependent (type II) diabetes mellitus. 174 94

Cardiovascular disease, and in particular ischemic heart disease, is the principal cause of morbidity, functional disability, and mortality in patients with non-insulin-dependent (type II) diabetes. The main risk factors for the macrovascular complications of diabetes are dyslipidemia, hypertension, and cigarette smoking. Although degree of hyperglycemia is a risk factor for microvascular complications, it is not a prominent risk factor for macrovascular complications. Nevertheless, there are theoretical reasons for believing that glycemic control could lower cardiovascular risk. For example, glycemic control may both improve clearance and suppress hepatic overproduction of very-low-density lipoprotein. Moreover, there is direct empirical evidence that improved glycemic control can favorably alter lipid profiles in type II diabetic patients. Despite this, the only clinical trial that has assessed cardiovascular mortality as an end point in diabetic subjects (i.e., the University Group Diabetes Program) failed to demonstrate a benefit of glycemic control. In this study, the insulin-variable group, which achieved sustained glycemic control relative to the placebo group, had essentially the same cardiovascular mortality as the latter group. All of the conventional lipid-lowering agents have been shown to produce favorable changes in lipid profiles in diabetic subjects. However, the optimum regimen remains to be defined. Metabolic differences between diabetic and nondiabetic subjects mean that the optimum lipid-lowering regimens for the two categories of patients may differ. For example, nicotinic acid, which is a powerful lipid-altering drug, may worsen glucose intolerance. The characteristic lipid abnormalities in type II diabetic subjects are hypertriglyceridemia and low high-density lipoprotein cholesterol, not hypercholesterolemia. Although the role of hypertriglyceridemia as a cardiovascular risk factor in the general population has been questioned, there is evidence that this lipid abnormality may play a stronger role in diabetic subjects. For all of the above reasons, there is an urgent need for large-scale clinical trials assessing cardiovascular end points and testing various strategies of improving lipid profiles in diabetic subjects, particularly given the fact that all of the current generation of lipid-lowering trials have systematically excluded diabetic patients.
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PMID:Dyslipidemia in type II diabetes. Implications for therapeutic intervention. 177 1

The incidence of cardiovascular disease in non-insulin-dependent diabetes mellitus (NIDDM) has not been reduced by the control of hyperglycemia alone. Hypertension and dyslipidemia may be the major determinants of macrovascular disease in these patients. With the high prevalence of hypertension in NIDDM, antihypertensive drugs are likely to be important determinants of an atherogenic lipid profile. To date, there is no completed major randomized controlled trial of antihypertensive treatment outcome in a diabetic population, and as such, drug choice for the treatment of diabetic hypertension is often based on evidence extrapolated from studies in nondiabetic groups. However, two short-term studies have assessed the effects of doxazosin antihypertensive therapy in subjects with NIDDM. Both studies showed that the significant reduction in blood pressure with doxazosin treatment was associated with favorable effects on the serum lipid profile. In one study, contrasting adverse effects of atenolol treatment on glycemic control, lipids, and lipoproteins were observed. Doxazosin therapy was associated with a trend toward correcting the disturbances of lipoprotein metabolism characteristic of NIDDM. These metabolic effects, combined with effective lowering of blood pressure by doxazosin, may be important determinants of cardiovascular disease in the long term.
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PMID:Doxazosin therapy in the treatment of diabetic hypertension. 182 86

Coronary heart disease is the leading cause of death among patients with non-insulin-dependent diabetes mellitus (NIDDM). NIDDM patients have a high frequency of dyslipidemia, which along with obesity, hypertension, and hyperglycemia may contribute significantly to accelerated coronary atherosclerosis. Because risk factors for coronary heart disease are additive and perhaps multiplicative, even mild degrees of dyslipidemia may enhance coronary heart disease risk. Therefore, therapeutic strategies for management of NIDDM should give equal emphasis to controlling hyperglycemia and dyslipidemia. The National Cholesterol Education Program recently issued guidelines for treatment of hyperlipidemia in adults including diabetic patients. Because of the unique features of diabetic dyslipidemia, however, we suggest that certain modifications in these guidelines be made to meet specific needs of diabetic patients. For example, therapeutic goals for serum cholesterol reduction should be lower in diabetic patients than in nondiabetic subjects. Particular emphasis should be given to weight reduction in NIDDM patients. In some diabetic patients, monounsaturated fatty acids may be a better replacement for saturated fatty acids than carbohydrates. The target for cholesterol lowering should include both very-low-density lipoprotein and low-density lipoprotein (LDL) (non-high-density lipoprotein) rather than LDL alone. To obtain a substantial reduction of cholesterol levels, drug therapy may be required in many patients. However, first-line drugs for nondiabetic patients (nicotinic acid and bile acid sequestrants) may be less desirable in NIDDM patients than hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors and even fibric acids. In fact, HMG CoA reductase inhibitors may be the drugs of choice for NIDDM patients with elevated LDL cholesterol and borderline hypertriglyceridemia, whereas gemfibrozil appears preferable for NIDDM patients with severe hypertriglyceridemia.
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PMID:Management of dyslipidemia in NIDDM. 219 Jul 70

The chronic hyperglycemia of non-insulin-dependent diabetes mellitus (NIDDM) evolves gradually and is usually preceded by more transient hyperglycemia, classified as impaired glucose tolerance (IGT). Already in this phase, there is an increased risk of cardiovascular complications, and many IGT subjects, like NIDDM patients, often display several of the metabolic and circulatory disturbances that are associated with hyperglycemia, e.g., insulin resistance, hyperinsulinemia and/or hyperproinsulinemia, delayed insulin release, dyslipidemia, and hypertension. Therefore, and because untreated hyperglycemia is a self-perpetuating condition, early detection and early intervention may be necessary to prevent the progression and complications of NIDDM. This in turn would necessitate screening procedures, and the therapeutic goal should include both euglycemia and normalization of plasma insulin, plasma lipids, and blood pressure. A study in the German Democratic Republic indicated that the mortality in screening-detected NIDDM patients did not differ from that in patients detected in routine care. In a Swedish study on screening-detected NIDDM subjects, only those who had IGT rather than manifest NIDDM could maintain fasting blood glucose less than or equal to 6 mM for 5 yr by hypocaloric dietary regulation alone. In those with screening-detected NIDDM, the delayed acute insulin release and net postprandial hyperglycemia were improved by addition of glipizide, and most managed to attain and maintain fasting blood glucose less than or equal to 6 mM for approximately 2 yr after such addition. However, after 4 yr, there was an increase in blood glucose, suggesting that preventive intervention either may not be possible or may have to start in the IGT phase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Will sulfonylurea treatment of impaired glucose tolerance delay development and complications of NIDDM? 220 45

Secondary failure to oral hypoglycemic agents occurs in some 5% of type II diabetic patients per year, such that treatment with insulin becomes warranted. In most of the cases only hyperglycemia is apparent, while signs of severe metabolic derangement such as thirst, polyuria and weight loss are lacking. However, the hyperglycemic state adversely affects endogenous insulin secretion and favors the development of microvascular complications and neuropathy. In addition, dyslipidemia is often present, and the patient's well-being may be impaired. To differentiate between real secondary drug failure and transient metabolic impairment due to insufficient compliance with the diet prescriptions, plasma C-peptide should be measured. Insulin therapy should be initiated with a dose of 6-8 IU of an intermediate-action preparation and subsequently adjusted based on blood glucose measurements. Frequently it will be necessary to employ twice daily a mixture of (rapid- and intermediate-action) insulin in order to achieve adequate control of postprandial hyperglycemia. In some cases insulin therapy can be discontinued since the endogenous insulin secretion may improve during insulin treatment. We do not recommend to use as initial therapy of patients with secondary failure to oral hypoglycemic agents a combination of sulfonylureas and insulin since the 'insulin-saving' effect is small and not cost-effective.
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PMID:[Insulin treatment of Type II diabetes]. 223 54


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