Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The blood monocytes adhere to endothelial cells unstimulated and after stimulation by interleukin-1, tumor necrosis factor or other mediators. This process is mediated through specific molecules on both endothelial cells and monocytes. Using specific monoclonal antibodies and molecular cloning several families of molecules involved in leukocyte endothelial cell interaction have been defined. Leukocyte adhesion molecules include the three beta 2 integrins (CD11/CD18 molecules), VLA-4 and the L-Selectin. E-Selectin (ELAM-1), P-Selectin (GMP-140) and receptors of the immunoglobulin superfamily (ICAM-1, ICAM-2 and VCAM-1) are expressed on endothelial cells in basal conditions and after activation. It has been shown that these adhesive molecules are involved in blood monocyte adhesion to endothelial cells. Monocytes from patients with diabetes mellitus had an increased adhesion to endothelial cells in culture. As estimated by flow cytometry CD11b/CD18 expression on diabetic monocytes was increased. Pentoxifylline reduced CD11b/CD18 expression on normal and diabetic monocytes. This effect was associated to a decrease in monocyte adhesion to endothelial cells.
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PMID:Molecular mechanism of blood monocyte adhesion to vascular endothelial cells. 134 May 30

Hypertriglyceridemia is not a common finding in well controlled patients with insulin dependent diabetes; however, in noninsulin dependent, or Type II diabetes, hypertriglyceridemia and coronary heart disease are a well recognized clinical triad. In the latter setting, hypertriglyceridemia is usually the result of an associated inherited hyperlipidemia, most commonly familial hypertriglyceridemia but also familial combined hyperlipidemia. In the former, one sees elevated triglycerides and a low HDL-cholesterol, in the latter the same phenotype may be present but often there is a high LDL-cholesterol. Irrespective of the pathogenesis of the primary hypertriglyceridemic disorder, the occurrence of poorly controlled diabetes will enhance the hypertriglyceridemia and even in the Type II diabetic, with triglycerides in the thousands, dietary and glycemic control, alone, will strikingly ameliorate the hypertriglyceridemia. In contrast to patients with hypercholesterolemia, no national guidelines have been proposed for the treatment of patients with hypertriglyceridemia. Yet both experimental and clinical data support an algorithm in which dietary and glycemic control are optimized with a resultant major improvement in triglycerides, followed by the introduction of drug therapy. Three agents are particularly useful in correcting the hypertriglyceridemia: gemfibrozil, niacin, and fish oils, with the first two having the added benefit of increasing HDL levels. Lovastatin is also useful in treating these patients, but primarily for lowering LDL-cholesterol while triglycerides are independently being brought under control. Correction of hyperlipidemia in diabetic patients can generally be achieved with judicious use of dietary, glycemic and drug therapy; however, maintenance of a favorable response requires a high level of patient compliance, which is usually difficult to sustain.
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PMID:Hypertriglyceridemia in diabetes. An approach to management. 176 54

Patients with non-insulin dependent diabetes mellitus have an increased incidence of coronary artery disease which may, in part, be associated with abnormalities in plasma lipids. In a double-blind, parallel, randomized study, lovastatin and gemfibrozil were compared in 102 diabetic patients with primary hypercholesterolemia; two-thirds of the patients were treated with oral hypoglycemic agents and one-third received diet therapy alone for their diabetes. Mean pretreatment total and low-density lipoprotein (LDL) cholesterol values were 273 and 193 mg/dl, respectively. Lovastatin significantly reduced total, LDL and very low density lipoprotein cholesterol (20, 26 and 28%, respectively) and raised high-density lipoprotein (HDL) cholesterol (14%). Gemfibrozil significantly reduced triglycerides and very low density lipoprotein cholesterol (36 and 41%, respectively) and, to a lesser extent, total cholesterol (9%); it also increased HDL cholesterol (21%). Lovastatin therapy was not associated with a significant change in triglycerides, and gemfibrozil did not significantly lower LDL cholesterol. The decrease in the ratio of total to HDL cholesterol tended to be greater with lovastatin than with gemfibrozil (26.5 and 20.4%, respectively; p = 0.053). Changes in lipid profiles with both agents were of a degree similar to those reported in nondiabetic patients. Neither agent had a clinically important effect on fasting glucose or hemoglobin A1c. Both drugs were well tolerated with the exception of 2 patients treated with gemfibrozil who developed symptoms of cholecystitis.
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PMID:Comparison of the effects of lovastatin and gemfibrozil on lipids and glucose control in non-insulin-dependent diabetes mellitus. 220 32

Hypertriglyceridemic patients with non-insulin-dependent diabetes mellitus (NIDDM) have an increased risk of coronary heart disease (CHD) and acute pancreatitis. To examine the potential of hypolipidemic drugs for therapy of lipoprotein abnormalities in NIDDM, 10 patients maintaining marked (plasma triglycerides greater than 500 mg/dl) and 6 with moderate (plasma triglycerides 250-500 mg/dl) hypertriglyceridemia, despite good glycemic control, were studied in two phases. In the first phase, gemfibrozil alone (600 mg twice daily) was compared with a placebo, and in the second phase a combination of gemfibrozil and lovastatin (20 mg twice daily) was compared with gemfibrozil alone in a randomized, double-blind, placebo-controlled crossover study. In markedly hypertriglyceridemic patients, gemfibrozil reduced plasma triglycerides by 52% and very-low-density lipoprotein cholesterol (VLDL-chol) by 55% and increased high-density lipoprotein cholesterol by 23% compared with a placebo. However, low-density lipoprotein cholesterol (LDL-chol) levels increased (42%), and LDL apolipoprotein B (apoB) levels remained unchanged. Addition of lovastatin to gemfibrozil effectively reduced total cholesterol (25%), LDL-chol (30%), and LDL-apoB (19%). Lovastatin further reduced plasma triglycerides (11%) and VLDL-chol (27%). However, in moderately hypertriglyceridemic patients, gemfibrozil or the combination therapy did not seem to offer benefits over the previously reported study with lovastatin alone. Glycemic control was maintained throughout the study. In conclusion, the beneficial effects of the combination therapy on lipoprotein levels in markedly hypertriglyceridemic NIDDM patients could decrease the risk of development of both acute pancreatitis and CHD.
Diabetes 1989 Mar
PMID:Gemfibrozil alone and in combination with lovastatin for treatment of hypertriglyceridemia in NIDDM. 291 1

Coronary heart disease is an important cause of death in patients with non-insulin-dependent diabetes mellitus (NIDDM) and is particularly common in diabetic populations that have relatively high levels of plasma cholesterol. To determine whether plasma cholesterol levels in patients with NIDDM could be reduced by drug therapy, we assessed the effect of lovastatin, a potent inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, in a randomized double-blind placebo-controlled manner in 16 white patients with NIDDM and mild to moderate elevations of plasma cholesterol. Lovastatin (20 mg twice daily) or a placebo was given for four weeks, during which blood glucose concentrations remained controlled. As compared with the placebo, lovastatin reduced total cholesterol by 26 percent, low-density lipoprotein (LDL) cholesterol by 28 percent, and LDL apolipoprotein B by 26 percent. Lovastatin therapy also reduced plasma triglycerides and very-low-density lipoprotein cholesterol by 31 percent and 42 percent, respectively. Although there was no change in the plasma level of high-density lipoprotein (HDL) cholesterol, the ratio of total cholesterol to HDL cholesterol fell by 29 percent. No side effects or abnormalities in serum values were noted during short-term lovastatin therapy. The beneficial effects of lovastatin on plasma lipid levels in patients with NIDDM could decrease the risk of the development of coronary heart disease.
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PMID:Lovastatin for lowering cholesterol levels in non-insulin-dependent diabetes mellitus. 342 5

In the past history of the pharmaceutical industry, secondary metabolites have been screened almost exclusively for antimicrobial activities. This biased and narrow view has severely limited the potential application of microbial metabolites. Fortunately, this situation is changing and we are now entering into a new era in which microbial metabolites are being applied to diseases heretofore only subjected to synthetic compounds. This new approach is the application of microbial secondary metabolites to diseases that are not caused by other bacteria or fungi. For years, major drugs such as hypotensive and anti-inflammatory agents that are used for non-infectious diseases have been strictly synthetic products. Similarly, major therapeutics for parasitic diseases in animals (for example, coccidiostats and anthelminthics) resulted strictly from screens of chemically synthesized compounds followed by molecular modification. However, today fermentation products such as monensin and lasalocid dominate the coccidiostat market. The avermectins, another group of streptomycete products, have high activity against helminths and arthropods. Indeed, their activity appears to be an order of magnitude greater than previously discovered anthelminthic agents, the vast majority of which are synthetic compounds. Umezawa's group in Japan has isolated many microbial products with important pharmacological activities by screening with simple enzymic assays. There is much interest in a natural inhibitor of intestinal glucosidase, which is produced by an actinomycete of the genus Actinoplanes. The aim is to decrease hyperglycaemia and triacylglycerol synthesis in adipose tissue, liver and the intestinal wall of patients with diabetes, obesity and type IV hyperlipidaemia. Another natural compound of interest is mevinolin, a fungal product which acts as a cholesterol-lowering agent in animals. Mevinolin is produced by Aspergillus terreus. In its hydroxyacid form (mevinolinic acid), mevinolin is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase from liver. It is clear that, although the microbe has contributed greatly to the benefit of mankind, we have merely scratched the surface of the potential of microbial activity.
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PMID:A new era of exploitation of microbial metabolites. 640 Apr 79

There is experimental evidence to suggest that hypercholesterolaemia may play a pathogenetic role in progressive glomerular injury. We investigated the effect of cholesterol-lowering therapy on the progression of diabetic nephropathy in 34 patients with non-insulin-dependent diabetes mellitus. Patients were randomly assigned in a single-blind fashion to treatment with either lovastatin, an HMG CoA reductase inhibitor (n = 16; mean dose 30.0 +/- 12.6 mg/day) or placebo (n = 18) for 2 years. Renal function was assessed by serially measuring the serum creatinine, glomerular filtration rate (using Cr51-EDTA), and 24-h urinary protein excretion. Lovastatin treatment was associated with significant reductions in total cholesterol (p < 0.001), LDL-cholesterol (p < 0.001) and apo B (p < 0.01), the reductions at 24 months being 26, 30 and 18%, respectively. Beneficial effects on serum triglyceride, HDL-cholesterol and apo A1 levels were also observed. Lp(a) showed no significant change in both groups. Glomerular filtration rate deteriorated significantly in the placebo group after 24 months (p < 0.025) but showed no significant change in the lovastatin-treated patients. The increase in serum creatinine was statistically significant (p < 0.02) in placebo-treated patients at 12 and 24 months, and in the lovastatin group after 24 months. Twenty-four hour urinary protein excretion increased in both groups (p < 0.05). Lovastatin treatment was not associated with significant elevations in liver or muscle enzymes. We conclude that effective normalisation of hypercholesterolaemia may retard the progression of diabetic nephropathy.
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PMID:Cholesterol-lowering therapy may retard the progression of diabetic nephropathy. 748 45

Familial combined hyperlipidemia (FCHL) is a common lipid disorder characterized by high levels of cholesterol, triglycerides, or both. The basic metabolic abnormality is overproduction of apolipoprotein B-100. High atherogenicity has been attributed to all forms of FCHL. We evaluated combined bezafibrate-lovastatin therapy in 10 patients (9 men and 1 woman) with FCHL and markedly high cholesterol and triglyceride levels who were at high risk of coronary artery disease and who had not responded to diet and bezafibrate treatment alone. Eight patients had coronary artery disease, 6 had hypertension, and 3 had noninsulin-dependent diabetes mellitus. Lovastatin 20 mg/day was added to the bezafibrate 600 mg/day regimen for 6 weeks; the lovastatin dosage was then doubled to 40 mg/day for an additional 6 weeks. The addition of 20 mg of lovastatin resulted in decreases of 15%, 20%, and 13% in total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels, respectively. Increasing the dose of lovastatin to 40 mg resulted in further moderate decreases of 4%, 3%, and 8% in total cholesterol, LDL cholesterol, and triglycerides, respectively, compared with the 20 mg/day dosage. Although previous reports have emphasized the potential side effects of combination treatment with lovastatin and fibric acid derivatives, our patients tolerated the regimen well, with no significant subjective complaints or laboratory abnormalities. The bezafibrate-lovastatin combination is a possible therapeutic option for severe, resistant FCHL, but close medical supervision is needed because of potential side effects.
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PMID:Treatment of severe, resistant familial combined hyperlipidemia with a bezafibrate-lovastatin combination. 851 43

Hyperlipidemia associated with non-insulin-dependent diabetes mellitus (NIDDM) and insulin resistance is characterized by high triglyceride levels; raised levels of total low-density lipoprotein (LDL), which is made up of small, dense, cholesterol-rich particles; low levels of high-density lipoprotein (HDL); and glycosylation of apolipoproteins. Optimal drug therapy for this lipid profile is controversial. To test whether a fibrinic acid derivative (gemfibrozil) or a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (lovastatin) would produce better results in these patients, a crossover study was performed. Gemfibrozil 600 mg twice daily and, after a washout period, lovastatin 20 to 40 mg twice daily were administered to nine patients with NIDDM. Gemfibrozil significantly decreased triglyceride, very-low-density lipoprotein (VLDL), and intermediate-density lipoprotein (IDL) levels, the total cholesterol:HDL ratio, and the IDL plus VLDL;HDL ratio, and significantly increased levels of HDL, HDL2, and HDL3. Lovastatin significantly decreased levels of total cholesterol, calculated LDL, directly measured LDL, IDL, total triglycerides, VLDL, and the ratios of LDL:HDL, total cholesterol:HDL, and directly measured LDL:HDL and significantly increased total HDL and HDL3 levels. Gemfibrozil was significantly more effective than lovastatin in raising total HDL and HDL3 levels and in lowering the IDL plus VLDL:HDL ratio. Lovastatin was significantly more effective than gemfibrozil in lowering total cholesterol, LDL, directly measured LDL, and the LDL:HDL and directly measured LDL:HDL ratios. In the absence of malignant hypertriglyceridemia, an HMG-CoA reductase inhibitor, rather than a fibrinic acid derivative, is indicated for the treatment of patients with dyslipidemia associated with NIDDM and insulin resistance.
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PMID:A comparison of lovastatin, an HMG-CoA reductase inhibitor, with gemfibrozil, a fibrinic acid derivative, in the treatment of patients with diabetic dyslipidemia. 859 42

Life limiting diabetes heart problems predominantly result from accelerated thrombogenesis superimposed on a localized arterial vessel stenosis (atherothrombosis). The atherosclerotic process is a slowly progressing vitious cycle of self-amplifying cell-cell interactions. Initially, corpuscular blood elements, predominantly monocytes adhere to locally activated endothelial cells, before they convert into lipid laden macrophages. The proliferative response of media smooth muscle cells to foam cell derived mediators proceeds to the fibrous plaque where underlying subendothelial matrix material activates bypassing platelets. The new concept of adhesion molecules explains how streaming white blood cells can locally adhere to the endothelial cells (selectin mediated), become triggered, stick (integrin mediated) and consecutively transmigrate. P-Selectin rapidly appears in the outer membrane of activated endothelial cells and platelets. It serves as receptor for sialic acid containing oligosaccharides within the monocyte/PMN membrane. These cells adhere to locally activated endothelium (nondenuding injury) and form nidus for the further adherence of activated platelets. Later, when platelets become activated in response to nuding endothelial injury, exposure of P-Selectin leads to the parallel local recruitment of white blood cells. Diabetic patients with clinically overt angiopathy, but also immediately after onset of the metabolic disease, were shown to have increased levels of circulating P-Selectin positive platelets. Therefore, it is suggested that enhanced platelet-leukocyte interaction might be pathogenetic for atherogenesis from the very beginning as it must be considered of importance for reperfusion injury and remodelling in a highly affected myocardium when the catastrophe of myocardial infarction has finally occurred.
Diabetes Res Clin Pract 1996 Feb
PMID:Adhesion molecules influencing atherosclerosis. 896 89


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