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Query: UMLS:C0011849 (diabetes)
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Diabetes mellitus is commonly associated with systolic and diastolic hypertension, and a wealth of epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. Thus, when hypertensive patients, whether obese or of normal body weight, are compared with age- and weight-matched normotensive controls, a heightened plasma insulin response to a glucose challenge is found consistently. A state of cellular resistance to insulin action subtends the observed hyperinsulinism. Using the insulin/glucose clamp technique in combination with tracer glucose infusion and indirect calorimetry, it has been demonstrated that the insulin resistance of essential hypertension is located in peripheral tissues (muscle), is limited to nonoxidative pathways of glucose disposal (glycogen synthesis), and correlates directly with the severity of hypertension. The reasons for the association of insulin resistance and essential hypertension can be sought in at least four general types of mechanisms: sodium retention, sympathetic nervous system overactivity, disturbed membrane ion transport, and proliferation of vascular smooth-muscle cells. Physiological maneuvers, such as caloric restriction (in the overweight patient) and regular physical exercise, can improve tissue sensitivity to insulin; good evidence indicates that these maneuvers also can lower blood pressure in both normotensive and hypertensive individuals. Insulin resistance and hyperinsulinemia also are associated with an atherogenic plasma lipid profile. Elevated plasma insulin concentrations enhance very-low-density lipoprotein (VLDL) synthesis, leading to hypertriglyceridemia. Progressive elimination of lipid and apolipoproteins from the VLDL particle leads to an increased formation of intermediate density and low-density lipoproteins, both of which are atherogenic. Last, insulin per se, independent of its effects on blood pressure and plasma lipids, is known to be atherogenic. The hormone enhances cholesterol transport into arteriolar smooth-muscle cells and increases endogenous lipid synthesis by these cells. Insulin also stimulates the proliferation of arteriolar smooth-muscle cells, augments collagen synthesis in the vascular wall, increases the formation of and decreases the regression of lipid plaques, and stimulates the production of a variety of growth factors. In summary, insulin resistance appears to be a syndrome that is associated with a clustering of metabolic disorders, including type II diabetes mellitus, obesity, hypertension, lipid abnormalities, and atherosclerotic cardiovascular disease.
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PMID:Insulin resistance, hyperinsulinemia, and coronary artery disease: a complex metabolic web. 128 37

Mounting data support a causal connection between high-normal fibrinogen levels and atherosclerotic cardiovascular disease. There is clearly a thrombogenic component to atherosclerosis and the onset of clinical manifestations. This offers the possibility to better identify high-risk candidates and also to protect them by reducing blood fibrinogen concentration or blocking its action. The relationship of antecedent fibrinogen to the subsequent development of cardiovascular disease is examined, based on 18 years of surveillance of a cohort of 1274 men and women aged 47 to 79 years who participated in the Framingham Study. The association with the development of peripheral arterial disease and cardiac failure is now examined in addition to previously studied relationships to coronary heart disease and stroke. In men and women, there is a significant age-adjusted relationship of fibrinogen level to coronary heart disease and to cardiovascular disease in general. In women, a significant relationship to cardiac failure and peripheral arterial disease, but not to stroke, was also found. These data on women are unique as they are not available elsewhere. Age-adjusted cardiovascular, all-cause, and coronary heart disease mortality were all related to fibrinogen in both sexes. In men, fibrinogen impact was the greatest for stroke and the least for peripheral arterial disease. For women, the impact on coronary heart disease was greatest. The absolute risk for an elevated fibrinogen level was greatest for coronary heart disease in both sexes. Average fibrinogen values are higher in women and in persons with other risk factors, including hypertension, cigarette smoking, diabetes, obesity, and elevated hematocrit. However, there is an independent contribution of fibrinogen to cardiovascular disease in general and coronary disease in particular, on adjustment for coexistent risk factors. Fibrinogen enhances the risk of cardiovascular disease in hypertensives, diabetics, and cigarette smokers. About half the cardiovascular risk of cigarette smoking appears due to the higher fibrinogen values. Now, five prospective studies document the excess incidence of cardiovascular events in persons with elevated fibrinogen levels within the "normal range." Each standard deviation increase in fibrinogen is associated with a 30% increment of coronary heart disease in men and a 40% increase in women. Fibrinogen should be added to the list of major cardiovascular risk factors. Trials of intervention to lower fibrinogen in high-risk coronary candidates are needed.
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PMID:Update on fibrinogen as a cardiovascular risk factor. 134 96

Raised urinary albumin excretion (UAE) is associated with an increased risk of cardiovascular disease in non-insulin-dependent diabetes mellitus (NIDDM). We have examined the role of endothelial dysfunction as a possible explanation for this association in 94 NIDDM patients by investigating UAE, new cardiovascular events, and plasma concentration of von Willebrand factor (vWF), an indicator of endothelial dysfunction. At baseline, 66 patients had normal UAE (less than 15 micrograms/min), which remained normal in 33 (group 1) and increased in 33 (to median 31.5 micrograms/min, group 2). In 28 patients, baseline UAE was abnormal (67.1 micrograms/min, group 3). Follow-up ranged between 9 and 53 months. vWF did not change in group 1 (median 128% at baseline and 123% at follow-up), but increased in group 2 (from 116 to 219%, p less than 0.0001) and group 3 (from 157 to 207%, p = 0.0005). Baseline level of and change in vWF were strongly related to the development of microalbuminuria (R2 = 0.60, p less than 0.0001), but cardiovascular risk factors were not (R2 = 0.14). Raised baseline UAE was associated with an increased risk of new cardiovascular events only in patients with vWF concentrations above the median (relative risk 3.66, 95% CI 1.3-11.9) and not in patients with lower vWF (0.19, 0.01-1.33). In addition, the cardiovascular risk associated with increased UAE was modified by low compared with high concentrations of serum high density lipoprotein cholesterol (2.86 [1.03-8.48] vs 0.15 [0.01-1.43]). Dysfunction of vascular endothelium may be a link between albuminuria and atherosclerotic cardiovascular disease in NIDDM.
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PMID:Urinary albumin excretion, cardiovascular disease, and endothelial dysfunction in non-insulin-dependent diabetes mellitus. 135 2

When adipose tissue enlarges in obesity, as the result of an imbalance between caloric intake and caloric expenditure, many changes occur in the cellular components of the adipose mass. A combination of increased cell size and number underlies the accretion of the adipose mass, however, only a reduction in cell size is possible with weight loss. Several metabolic abnormalities accompany obesity--most important--hyperinsulinemia, hyperlipidemia, insulin resistance, and carbohydrate intolerance. Clinical consequences of obesity include hypertension, venous insufficiency, gallbladder disease, osteoarthritis, pulmonary and cardiovascular insufficiency, diabetes, and atherosclerotic cardiovascular disease, and all are dependent on the severity and duration of the obesity. Once established, obesity is difficult to correct because of the development of many adaptive mechanisms by which obesity defends itself.
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PMID:Cellular, metabolic, and clinical consequences of adipose mass enlargement in obesity. 180 21

Prospective data was recorded on 217 percutaneous transluminal angioplasty (PTA) procedures performed in the superficial femoral and popliteal arteries over an 8-year period. After the initial procedure, patients were followed with serial noninvasive studies and, in 71 patients, repeat angiography. The mean follow-up period was 7 years (range, 2-11 years). Standard life-table survival analysis was used to assess the factors potentially affecting long-term outcome. Excluding an initial technical failure rate of 10%, overall patencies at 1, 3, and 5 years were 81%, 61%, and 58%, respectively. After the first year, the prognosis (i.e., failure rate) appears to be linear over the long term (i.e., up to 10 years). Factors negatively influencing long-term patency include the presence of diabetes mellitus, diffuse atherosclerotic cardiovascular disease, or threatened limb loss. Technical factors correlated with failure include lesion length, moderate eccentricity, and a poor post-PTA appearance.
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PMID:Femoropopliteal angioplasty. Factors influencing long-term success. 182 50

The association of obesity with hypertension has been amply demonstrated in cross-sectional, longitudinal, and dietary-intervention studies, but the mechanisms remain enigmatic. Both conditions are independently characterized by similar metabolic alterations, i.e., glucose intolerance, dyslipoproteinemia, elevated serum uric acid, and inadequate Na+ transport. Obesity, hypertension, and these metabolic alterations are associated with hyperinsulinemia/insulin resistance. The degree of these alterations is lowest in lean hypertensives, intermediate in obese normotensives, and greatest in obese hypertensives, but mortality risk is highest in lean hypertensives. This apparent discrepancy may be related to the divergent hemodynamic characteristics, possibly indicating different etiology, of lean and obese hypertensives, i.e., contracted blood volume, increased total vascular peripheral resistance, and normal sympathetic drive in the former, expanded blood volume, normal peripheral resistance, and increased sympathetic drive in the latter. Current knowledge suggests that the interrelationships of obesity and hypertension with the metabolic alterations could be mediated by high carbohydrate and fat consumption and low physical activity, resulting in obesity and separate pathways in hyperinsulinemia and increased sympathetic drive, leading to a double vicious cycle. In one, hyperinsulinemia and the consequent insulin resistance would compound one another. In the second, the increasing hyperinsulinemia would increasingly stimulate the sympathetic nervous system. This double vicious cycle could result in increasing hemodynamic and metabolic derangements causing hypertension, diabetes, and atherosclerotic cardiovascular disease (ASCVD). The association of lean hypertension with ASCVD may be through other mechanisms, e.g., hemodynamic forces on the vascular endothelium.
Diabetes Care 1991 Jun
PMID:Hyperinsulinemia or increased sympathetic drive as links for obesity and hypertension. 186 20

Abnormalities of plasma lipid and lipoprotein concentrations are common in both insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus. In general, individuals with IDDM who are untreated or inadequately treated have elevations in both postprandial and fasting triglyceride levels in association with reduced activity of lipoprotein lipase. Low-density lipoprotein (LDL) cholesterol levels can rise when insulin deficiency impacts on LDL-receptor function. When patients with IDDM are treated and plasma glucose levels well controlled, plasma very-low-density lipoprotein (VLDL) triglyceride and LDL cholesterol levels are usually normal. In addition, plasma high-density lipoprotein (HDL) cholesterol levels are normal or elevated in well-controlled IDDM subjects. In NIDDM, increased VLDL triglyceride and reduced HDL cholesterol concentrations are common and are only partially related to glycemic control. Overproduction of VLDL leads to hypertriglyceridemia, which can be exacerbated if lipoprotein lipase activity is also reduced. The regulation of LDL levels is complex; catabolism can be reduced if significant insulin deficiency exists or increased if significant hypertriglyceridemia is present. The reduced levels of HDL cholesterol in NIDDM appear to be related to increased exchange of HDL cholesteryl esters for VLDL triglycerides, although other mechanisms may exist. The roles of insulin resistance, obesity, and independently inherited abnormalities of lipoprotein metabolism in the etiology of dyslipidemia of NIDDM are complex and require further investigation. Finally, the effects of diabetes on glycosylation of apoproteins; on other lipid enzymes, particularly hepatic triglyceride lipase; on lipoprotein surface lipids; and on hepatic uptake of remnants have only just begun to be defined. In view of the marked increase in atherosclerotic cardiovascular disease in individuals with diabetes mellitus, prompt attention to and aggressive therapy for dyslipidemia should be a central component of care for these patients.
Diabetes Care 1991 Sep
PMID:Lipoprotein physiology in nondiabetic and diabetic states. Relationship to atherogenesis. 195 76

Epidemiologic research indicates that glucose intolerance and hypertension are interrelated phenomena, each powerfully predisposing to atherosclerotic cardiovascular disease. Both diabetic and hypertensive patients have greater amounts of atherogenic risk factors, including dyslipidemia, hyperuricemia, elevated fibrinogen, and left ventricular hypertrophy. Diabetic persons have an increased prevalence of hypertension (50%), and glucose intolerance is more common in hypertension (15% to 18%). Both share a strong relationship to excess weight, but the excess of hypertension in diabetic persons occurs in both lean and obese subjects. Diabetes doubles the risk of hypertension associated with overweight. The risk of coronary disease, stroke, and peripheral arterial disease increases with increasing blood pressure to the same degree in diabetic persons as in nondiabetic persons, but at any level of blood pressure, diabetic persons have a doubled risk of these outcomes. Both diabetic and hypertensive patients are particularly prone to silent or unrecognized myocardial infarctions. Greater efforts at primary prevention of both hypertension and diabetes are clearly needed, including efforts at weight control, exercise, limitation of salt intake, and control of blood lipid levels. In either diabetic or hypertensive candidates for cardiovascular disease, optimization of the chances of avoiding sequelae requires a comprehensive multifactorial approach. Prevention requires more than normalization of either the blood sugar or blood pressure. Rational preventive measures must also include weight reduction, a fat-modified diet, cessation of smoking cigarettes, raising high-density lipoprotein, lowering low-density lipoprotein, and reduction of fibrinogen. Hypertension, obesity, insulin resistance, hyperinsulinemia, hypertriglyceridemia, and low high-density lipoprotein cholesterol tend to coexist.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The epidemiology of impaired glucose tolerance and hypertension. 200 55

Diabetes mellitus is commonly associated with systolic/diastolic hypertension, and a wealth of epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. Thus, when hypertensive patients, whether obese or of normal body weight, are compared with age- and weight-matched normotensive control subjects, a heightened plasma insulin response to a glucose challenge is consistently found. A state of cellular resistance to insulin action subtends the observed hyperinsulinism. With the insulin/glucose-clamp technique, in combination with tracer glucose infusion and indirect calorimetry, it has been demonstrated that the insulin resistance of essential hypertension is located in peripheral tissues (muscle), is limited to nonoxidative pathways of glucose disposal (glycogen synthesis), and correlates directly with the severity of hypertension. The reasons for the association of insulin resistance and essential hypertension can be sought in at least four general types of mechanisms: Na+ retention, sympathetic nervous system overactivity, disturbed membrane ion transport, and proliferation of vascular smooth muscle cells. Physiological maneuvers, such as calorie restriction (in the overweight patient) and regular physical exercise, can improve tissue sensitivity to insulin; evidence indicates that these maneuvers can also lower blood pressure in both normotensive and hypertensive individuals. Insulin resistance and hyperinsulinemia are also associated with an atherogenic plasma lipid profile. Elevated plasma insulin concentrations enhance very-low-density lipoprotein (VLDL) synthesis, leading to hypertriglyceridemia. Progressive elimination of lipid and apolipoproteins from the VLDL particle leads to an increased formation of intermediate-density and low-density lipoproteins, both of which are atherogenic. Last, insulin, independent of its effects on blood pressure and plasma lipids, is known to be atherogenic. The hormone enhances cholesterol transport into arteriolar smooth muscle cells and increases endogenous lipid synthesis by these cells. Insulin also stimulates the proliferation of arteriolar smooth muscle cells, augments collagen synthesis in the vascular wall, increases the formation of and decreases the regression of lipid plaques, and stimulates the production of various growth factors. In summary, insulin resistance appears to be a syndrome that is associated with a clustering of metabolic disorders, including non-insulin-dependent diabetes mellitus, obesity, hypertension, lipid abnormalities, and atherosclerotic cardiovascular disease.
Diabetes Care 1991 Mar
PMID:Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. 204 34

Screening for dyslipoproteinemias should be undertaken in all individuals older than 20 years of age at least once every 5 years. The initial screening, as recommended by the Adult Treatment Guidelines Panel of the National Cholesterol Education Program, is to determine the concentration of total blood cholesterol. This initial determination can be made on blood obtained in the nonfasting state. Further evaluation of the patient's lipoprotein concentrations is dependent upon the presence of other cardiovascular risk factors. in the absence of definite coronary heart disease, hypertension, diabetes mellitus, a family history of coronary artery disease, cigarette smoking, or severe obesity, the patient with a total blood cholesterol concentration less than 200 mg/dL requires no specific instruction and should have a repeated screening performed within 5 years. Patients with blood cholesterol concentrations greater than 200 mg/dL should have their lipoprotein profiles determined if they have atherosclerotic cardiovascular disease or two other cardiovascular disease risk factors. The lipoprotein profile includes the determination of fasting cholesterol and triglyceride and HDL cholesterol concentrations. From these values, the LDL cholesterol concentration can be calculated. This LDL cholesterol concentration is central in selecting the appropriate therapy. HDL cholesterol concentrations may be useful in evaluating patients with ischemic heart disease. Concentrations of HDL cholesterol less than 35 mg/dL are associated with increased risk for coronary artery disease. Although there is currently no convincing evidence that support the specific treatment of depressed HDL cholesterol concentrations, therapy directed to modulating lipoprotein metabolism in patients with heart disease and low HDL concentrations may be of benefit. Patients with recurrent abdominal pain, pancreatitis, and eruptive xanthomatosis frequently have fasting hypertriglyceridemia concentrations exceeding 1000 mg/dL. These patients should be identified in order to effectively reduce their triglyceride concentrations, which can prevent these complications.
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PMID:Detection and evaluation of dyslipoproteinemia. 219 76


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