Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Insulin resistance, hyperinsulinemia, and coronary artery disease: a complex metabolic web. 128 37

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.
 ...
PMID:Lipoprotein physiology in nondiabetic and diabetic states. Relationship to atherogenesis. 195 76

It is now well recognized that insulin resistance and/or hyperinsulinemia are characteristic of a number of common human disease states including obesity, non-insulin dependent diabetes mellitus (NIDDM), essential hypertension, and atherosclerotic cardiovascular disease. More recent evidence suggests that impaired insulin action and elevated levels of circulating insulin may also be present in a substantial proportion of apparently healthy nonobese individuals. Considerable attention is now being focused on the potential long term adverse consequences of elevated circulating insulin levels. In particular, the frequent concurrence of these clinical disorders of carbohydrate metabolism, lipid metabolism, and vascular disease has led to the hypothesis that insulin resistance and the ensuing hyperinsulinemia may be a common pathophysiologic factor in the etiology of these disease states. In this review, we will examine the evidence for this hypothesis with particular attention to the adverse effects of chronic hyperinsulinemia.
 ...
PMID:Hyperinsulinemia and its sequelae. 220 24

Patients with non-insulin dependent diabetes mellitus (NIDDM) have a higher risk of atherosclerotic cardiovascular disease than nondiabetic subjects. In seven patients with both hypercholesterolemia and NIDDM controlled by chlorpropamide, lovastatin (20 mg b.i.d. for 6 weeks) lowered low-density lipoprotein cholesterol by 28%, total cholesterol by 24%, and apolipoprotein B by 24%. Lovastatin levels for a 4-hour period (measured as 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitory activity) were similar to those measured previously in nondiabetic patients. Lovastatin did not alter chlorpropamide kinetics or glycemic profiles. No patient had an elevation in serum transaminases or creatinine phosphokinase, and no patient had any other laboratory or clinical drug-related adverse experience during the study. Lovastatin was as effective in reducing low-density lipoprotein cholesterol in patients with NIDDM as in nondiabetic subjects. Diabetic control was unaltered, and no evidence of alteration in lovastatin or chlorpropamide blood levels was noted.
 ...
PMID:Effects of lovastatin in diabetic patients treated with chlorpropamide. 222 7

A case of anaerobic sepsis associated with Fusobacterium mortiferum is reported. Blood cultures from a 60-year-old man with type II diabetes mellitus, hypertension, severe atherosclerotic cardiovascular disease, and renal insufficiency revealed on a gramstained smear highly pleomorphic gram-negative bacilli with bizarre forms and round bodies. Growth of the organism on nonselective anaerobic media and analysis of its pattern produced results characteristic of Fusobacterium mortiferum.
 ...
PMID:Anaerobic septicemia secondary to Fusobacterium mortiferum. 371 72

Hyperinsulinemia is very much in the spotlight. Debate rages as to its significance and role in the etiology not only of NIDDM, but also other morphological and metabolic risk factors for atherosclerotic cardiovascular disease, including upper-body obesity, dyslipidemia, hypertension, and hyperuricemia. Epidemiological data support a key role for hyperinsulinemia in these disorders but it is far from conclusive except for the fact that hyperinsulinemia and insulin resistance may be present many years before the onset of impaired glucose tolerance and NIDDM, and clearly play a role in their etiology. The thrifty genotype hypothesis provides a plausible basis for a better understanding of how hyperinsulinemia and insulin resistance could lead to glucose intolerance and atherosclerotic cardiovascular disease, but the detailed biochemical mechanisms remain elusive. A role for increased sympathetic nervous system activity, resulting from hypothalamic stimulation as a primary event causing hyperinsulinemia, cannot be excluded as a cause of hyperinsulinemia. The current focus on hyperinsulinemia also has resulted in closer examination of the therapy of diabetes and hypertension, emphasizing the need to avoid hyperinsulinemia in both IDDM and NIDDM individuals because of the putative risk of atherosclerotic cardiovascular disease and hypertension. There is still a paucity of epidemiological data to support a role for hyperinsulinemia in the etiology of hypertension. However, clinical practice already is being influenced by the fact that ACE inhibitors have been shown to reduce insulin resistance in clinical research studies. The research reviewed here, particularly that relating to hyperinsulinemia, insulin resistance, and cardiovascular disease risk factors, has opened new vistas for the treatment and prevention of NIDDM and atherosclerotic cardiovascular disease. Appropriate exercise clearly is associated with improved insulin sensitivity, modification of CVD risk factors, and lower prevalence of NIDDM. Upper-body obesity, the latest culprit in the field, can also be reduced by exercise. Hyperinsulinemia and insulin resistance can be detected in children, adolescents, and young adults. NIDDM can be prevented, but clearly, intervention needs to commence in childhood, and intensive risk factor intervention in subjects with NIDDM can reduce the risk of atherosclerotic cardiovascular disease. It seems paradoxical that prevention of NIDDM and atherosclerotic cardiovascular disease are now possible even though the biochemical and molecular basis of these disorders is not fully understood.
 ...
PMID:Hyperinsulinemia--how innocent a bystander? 829 79

Subtle abnormalities of carbohydrate metabolism and overt diabetes mellitus are both associated with a substantial increase in the prevalence of hypertension and the accelerated development of atherosclerosis. Hypertension is also a presumed independent risk factor for atherosclerosis, although some of the atherogenic properties of hypertension may be related to the recently recognized subtle metabolic abnormalities commonly found in persons with essential hypertension. The results of epidemiologic studies suggest that the elevated fasting and postprandial insulin levels that often occur in patients with essential hypertension, as well as in patients with type II diabetes mellitus, are an independent risk factor for atherosclerotic cardiovascular disease. Elevated glucose levels in patients with diabetes and hypertension appear to contribute to the acceleration of atherosclerosis, perhaps through toxic effects on the vascular endothelium. Other cardiovascular risk factors that are accentuated in persons with carbohydrate intolerance and hypertension include abnormalities in platelet function, clotting factors, the fibrinolytic system, and dyslipidemia. The goals of both nonpharmacologic and pharmacologic therapy for patients with abnormal carbohydrate metabolism and hypertension are to decrease cardiovascular risk as well as lower blood pressure.
 ...
PMID:Hyperinsulinemia, insulin resistance, and hyperglycemia: contributing factors in the pathogenesis of hypertension and atherosclerosis. 839 10

To assess the prevalence of an impaired diurnal blood pressure (BP) pattern in a population of both normotensive and hypertensive diabetics, noninvasive ambulatory BP monitoring (SpaceLabs 5200, Redmond, WA) was performed in 96 outpatients with type 2 diabetes (47 normotensives and 48 hypertensives) and in 103 control subjects without diabetes (50 normotensives and 53 hypertensives). Mean 24 h and daytime (06:00 to 22:00) BP and heart rate (HR) were not statistically different in diabetic patients compared to nondiabetic ones. Nighttime (22:00 to 06:00) BP and HR tended to be higher in both normotensive and hypertensive diabetics, although not significantly. Heart rate, diastolic BP (DBP), and especially the nocturnal systolic BP (SBP) decrease, were less marked in both normotensive and hypertensive diabetics, with a consequent increase in rate-pressure. A significant correlation was found between the percent decrease in nighttime SBP and the decrease in orthostatic SBP in casual BP measurements. The analysis of individual recordings allowed us to detect an impaired circadian pattern (the disappearance of the nocturnal BP decrease or a paradoxical BP increase) in 30% of the normotensive and 31% of the hypertensive diabetics (v 6% of the normotensive and 6.4% of the hypertensive nondiabetic subjects). As the absence of a nocturnal BP fall has been associated with the increased prevalence of left ventricular hypertrophy and atherosclerotic cardiovascular disease, its detection by ambulatory monitoring might be of prognostic and therapeutic importance.
 ...
PMID:Ambulatory blood pressure monitoring in normotensive and hypertensive type 2 diabetes. Prevalence of impaired diurnal blood pressure patterns. 842 56

Insulin resistance confers increased susceptibility to NIDDM, atherosclerotic cardiovascular disease, ovarian hyperandrogenism, and possibly hypertension. Insulin resistance is largely inherited, in rare cases as a monogenic disorder or more commonly as a complex trait. The search for insulin resistance genes relies mainly on two complementary approaches: 1) positional cloning using random DNA markers present throughout the genome; and 2) the analysis of specific candidate genes. This report briefly summarizes the candidate gene approach to insulin resistance. Progress related to the analysis of genes encoding molecules that participate in insulin action is reviewed. In addition, the spectrum of potential genetic defects that might contribute to insulin resistance, both at the level of the target cell and secondarily (e.g., obesity genes), is discussed.
 ...
PMID:Candidate genes for insulin resistance. 872 72

Atherosclerotic cardiovascular disease is the major cause of morbidity and mortality in NIDDM patients. But the exact pathophysiology of accelerated atherosclerosis seen in NIDDM is not completely understood. Hyperinsulinemia and hyperlipidemia frequently coexist in these subjects. Present study was undertaken to demonstrate relationship of serum insulin with atherogenic lipids in 92 (male = 62, female = 30) newly diagnosed, middle-aged, nonsmoking, uncomplicated and untreated NIDDM patients with normal body mass index (BMI). Fourty (male = 20, female = 20) non-diabetic healthy subjects with a negative family history of diabetes served as control. After an overnight fasting, venous blood was collected for plasma glucose, serum insulin and lipid profile. ECG and oral glucose tolerance test (OGTT) were done in all subjects. Diabetes mellitus was diagnosed by WHO criteria. Total cholesterol, LDL-c, LDL/HDL ratio, TG (p always < 0.001) and fasting serum insulin (p = 0.033) were significantly higher and HDL-c was significantly lower (p = 0.001) in NIDDM than control subjects. Fasting serum insulin was inversely related to the degree of hyperglycemia in NIDDM subjects (r = -0.1867; p = 0.037). NIDDM with hyperinsulinemia (n = 18) had a strong negative correlation (r = -0.449, p = 0.031) with HDL-c. Neither total cholesterol nor LDL-c had any significant correlation with insulin. The results indicate that diabetic state itself is associated with atherogenic lipid disorder.
 ...
PMID:Lipid profile and its relation to fasting insulin level in non-insulin dependent diabetes mellitus (NIDDM). 881 64


1 2 3 4 5 6 7 8 9 10 Next >>