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)

Resorption inhibitors for cholesterol are commonly applied today in case of hypercholesterolemia in addition to statins. This combination therapy reduces the value of the LDL concentration by 50-60%. A target value of 100 mg/dl should be adjusted in case of high-risk patients in order to also decrease coronary risk. The significance of the triglycerides level is also becoming increasingly important, for it describes a high cardiovascular risk due to an increase of adiposity and diabetes. Such a dysfunction in storage and release of fatty lipids from triglycerides is treated dependent on severity: Patients with slightly elevated values (> 200 mg/dl) should change their habits (e.g. balanced diet, abstinance of alcohol, exercise) if necessary followed by application of fibrates, omega-3 fatty acids or nicotinic acid. These medicamentous measures are inevitable and must be applied immediately in case patients having values >1000 mg/dl.
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PMID:[Lipometabolic disorder--cholesterol and triglycerides]. 1701 80

The metabolic syndrome or cardiovascular dysmetabolic syndrome is characterized by obesity, central obesity, insulin resistance, atherogenic dyslipidemia, and hypertension. The major risk factors leading to this syndrome are physical inactivity and an atherogenic diet and cornerstone clinical feature is abdominal obesity or adiposity. In addition, patients usually have elevated triglycerides, low HDL cholesterol, elevated LDL cholesterol, other abnormal lipid parameters, hypertension, and elevated fasting blood glucose. Impaired fibrinolysis, increased susceptibility to thrombotic events, and raised inflammatory markers are also observed. Given that India has the largest number of subjects with type-2 diabetes in the world it can be extrapolated that this country also has the largest number of patients with the metabolic syndrome. Epidemiological studies confirm a high prevalence. Therapeutic approach involves intervention at a macro-level and control of multiple risk factors using therapeutic lifestyle approaches (diet control and increased physical activity, pharmacotherapy - anti-obesity agents) for control of obesity and visceral obesity, and targeted approach for control of individual risk factors. Pharmacological therapy is a critical step in the management of patients with metabolic syndrome when lifestyle modifications fail to achieve the therapeutic goals. Anti-obesity drugs such as sibutramine and orlistat can be tried to reduce weight and central obesity and jointly control the metabolic syndrome components. Other than weight loss, there is no single best therapy and treatment should consist of treatment of individual components of the metabolic syndrome. Newer drugs such as the endocannabinoid receptor blocker,rimonabant, appear promising in this regard. Atherogenic dyslipidemia should be controlled initially with statins if there is an increase in LDL cholesterol. If there are other lipid abnormalities then combination therapy of statin with fibrates, nicotinic acid, or ezetimibe should be considered. For insulin resistance, drugs such as thiazolidinediones and renin-angiotensin system blockers are available. Available evidence suggests that angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBS) may be more beneficial for treatment of hypertension in patients with metabolic syndrome compared to others as these drugs also prevent development of diabetes. Patients with metabolic syndrome also have elevations in fibrinogen and other coagulation factors leading to prothrombotic state and aspirin may be beneficial for primary prevention in these patients. The new developments in the treatment of metabolic syndrome with drugs, such as peroxisome proliferator-activated receptor (PPAR) agonists and cannabinoid receptor-1 antagonists, will broaden the horizons of the current treatment options. Fixed-dose combination polypharmacy using a single pill is an interesting concept that needs to be evaluated in long-term prospective trials in such patients.
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PMID:Management issues in the metabolic syndrome. 1721 77

Patients with type 2 diabetes have a marked increase in the risk of premature coronary heart disease (CHD). One of the underlying reasons for this increased risk is atherogenic dyslipidaemia, which is common in this patient group and characterized by low plasma levels of high-density lipoprotein cholesterol (HDL-C), increased levels of serum triglycerides, specifically very low-density lipoprotein triglycerides, and an increase in small, dense low-density lipoprotein (LDL) particles. Current management strategies focus on the initial use of statin or fibrate therapy (the latter approach indicated in patients with pronounced hypertriglyceridaemia). Recent treatment guidelines also emphasize the need for reduction in LDL-cholesterol (LDL-C) below 100 mg/dl (2.6 mmol/l) in diabetic patients, as this patient group has a clustering of cardiovascular risk factors that collectively lead to an excess risk of premature mortality. Multidrug lipid-modifying therapy has been proposed to further reduce CHD risk in diabetic patients. Adding nicotinic acid to primary statin therapy would be a logical approach based on the complementary therapeutic benefits of these treatments. Nicotinic acid is the most potent agent currently available for raising HDL-C and is also effective in reducing triglycerides and LDL-C. Moreover, clinical trial data have shown that nicotinic acid can be safely used in diabetic patients. Data from the Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER 2) study in patients with established CHD and low HDL-C (27% of whom had type 2 diabetes) show the atheroprotective effects of nicotinic acid/statin combination therapy. The clinical benefits of this combination therapy are indicated by subgroup analyses from the HDL-Atherosclerosis Treatment Study, which showed 40% reduction in coronary event frequency in patients with impaired glucose tolerance. Together, these data support the proposed strategy of aggressive multidrug treatment of diabetic dyslipidaemia to improve patient outcome.
Diabetes Obes Metab 2007 Sep
PMID:Dyslipidaemia in diabetic patients: time for a rethink. 1769 54

The mitochondrial pyruvate dehydrogenase complex (PDC) is inactivated in many tissues during starvation and diabetes. We investigated carbohydrate oxidation (CHO) and the regulation of the PDC in lean and obese Zucker diabetic fatty (ZDF) rats during fed and starved conditions as well as during an oral glucose load without and with pharmacologically reduced levels of free fatty acids (FFA) to estimate the relative contribution of FFA on glucose tolerance, CHO, and PDC activity. The increase in total PDC activity (20-45%) was paralleled by increased protein levels ( approximately 2-fold) of PDC subunits in liver and muscle of obese ZDF rats. Pyruvate dehydrogenase kinase-4 (PDK4) protein levels were higher in obese rats, and consequently PDC activity was reduced. Although PDK4 protein levels were rapidly downregulated (57-62%) in both lean and obese animals within 2 h after glucose challenge, CHO over 3 h as well as the peak of PDC activity (1 h after glucose load) in liver and muscle were significantly lower in obese rats compared with lean rats. Similar differences were obtained with pharmacologically suppressed FFA by nicotinic acid, but with significantly improved glucose tolerance in obese rats, as well as increased CHO and delta increases in PDC activity (0-60 min) both in muscle and liver. These results demonstrated the suppressive role of FFA acids on the measured parameters. Furthermore, the results clearly demonstrate a rapid reactivation of PDC in liver and muscle of lean and obese rats after a glucose load and show that PDC activity is significantly lower in obese ZDF rats.
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PMID:Dysregulated pyruvate dehydrogenase complex in Zucker diabetic fatty rats. 1795 38

With an increasing number of studies describing the negative correlation of coffee consumption and the risk for type 2 diabetes mellitus, we were compelled to elucidate the nutrients which bring pharmacological effects on risk reduction for diabetes. In this review, the author's interest is focused on chlorogenic and caffeic acids derived from lightly roasted coffee beans, as well as nicotinic acid, volatile Maillard reaction products (vMRPs), and another structurally unknown compound contained in heavily roasted beans. Caffeine is a common compound in both lightly and heavily roasted beans and its anti-inflammatory effects on degenerative diseases such as diabetes mellitus has been reevaluated recently. The prophylactic effects of coffee on diabetes involve pleiotropy of plural components in accordance to the degree of the roasting. A new concept of nutritional blended coffee may be important to optimize the prophylactic effects of coffee on lowering the risk factors of diabetes and delaying the progress of diabetes complications as well.
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PMID:[Pharmacological bases of coffee nutrients for diabetes prevention]. 1797 58

Type 2 diabetes mellitus and the closely related metabolic syndrome markedly increase the risk of cardiovascular disease a major contributor is the dyslipidemia. Recent studies and new national guidelines suggest these very high risk patients with cardiovascular disease achieve optional low density lipoprotein cholesterol (LDL-C) level of less than 70 mg/dl. In addition there may be no threshold to begin therapeutic lifestyle change and pharmacologic therapy to reduce LDL-C by 30-40%. Although randomized controlled trials with statins indicate that LDL reduction clearly reduces cardiovascular risk in these patients, the typical dyslipidemia of type 2 diabetes mellitus is also characterized by low high density lipoprotein cholesterol (HDL-C) levels, increased triglyceride-rich lipoproteins and small dense LDL, as well as increased postprandial lipemia. The later lipoproteins increase non-HDL-C levels. In order to address these abnormalities it may be necessary to utilize combined approaches with a fibrate or nicotinic acid, or other agents with statins to help reduce risk beyond statins. In addition, supervised, therapeutic life-style change is often underutilized therapy in patients with established coronary artery disease. This review will focus on maximizing the treatment of dyslipidemia in type 2 diabetes and the metabolic syndrome and discuss the evidence based studies and new developments in the management in these very high risk patients.
Curr Diabetes Rev 2005 May
PMID:Cardiovascular disease risk of type 2 diabetes mellitus and metabolic syndrome: focus on aggressive management of dyslipidemia. 1822 May 88

Niacin (nicotinic acid), the most effective available pharmacotherapy for increasing high-density lipoprotein cholesterol, also lowers triglycerides and hence may be useful, alone or in combination with hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), to offset residual cardiovascular risk in patients with mixed or diabetic dyslipidemia. We conducted a review of published consensus guidelines since 2000 and an English-language PubMed search of prospective, randomized controlled trials and open-label studies from January 1, 1990, through December 31, 2007, concerning the effects of niacin, alone or in combination with statins, on glycemic regulation in dyslipidemic patients (with or without diabetes mellitus). For search terms, we used the title words niacin or nicotinic acid and key words including diabetes, diabetic, dyslipidemia, glucose, glycemic, HbA1c, hemoglobin, hyperglycemia, human, insulin, postprandial, and safety. Retrospective and observational studies, case reports, and case studies were excluded. On the basis of our analysis, the effects of niacin (< or =2.5 g/d), alone or in combination with statins, on fasting glucose (an increase of 4%-5%) and hemoglobin A1c levels (an increase of < or =0.3%) are modest, transient or reversible, and typically amenable to adjustments in oral hypoglycemic regimens without discontinuing niacin. Niacin therapy was infrequently associated with incident diabetes or the need for new insulin prescriptions. Studies showed important clinical benefits of niacin or niacin-statin regimens despite modest effects on glucose control. On a population basis, significant reductions in incidences of cardiovascular events and the degree of atherosclerotic progression associated with long-term niacin (or niacin-statin) therapy in patients with diabetic dyslipidemia outweigh the typically mild effects of this therapy on glycemic regulation. Consensus guidelines recommend monitoring glycemic control after initiating niacin treatment or increasing its dosage.
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PMID:Effects of niacin on glucose control in patients with dyslipidemia. 1838 Sep 93

Unbalanced diets generate oxidative stress commonly associated with the development of diabetes, atherosclerosis, obesity and cancer. Dietary flavonoids have antioxidant properties and may limit this stress and reduce the risk of these diseases. We used a metabolomic approach to study the influence of catechin, a common flavonoid naturally occurring in various fruits, wine or chocolate, on the metabolic changes induced by hyperlipidemic diets. Male Wistar rats ( n = 8/group) were fed during 6 weeks normolipidemic (5% w/w) or hyperlipidemic (15 and 25%) diets with or without catechin supplementation (0.2% w/w). Urines were collected at days 17 and 38 and analyzed by reverse-phase liquid chromatography-mass spectrometry (LC-QTOF). Hyperlipidic diets led to a significant increase of oxidative stress in liver and aorta, upon which catechin had no effect. Multivariate analyses (PCA and PLS-DA) of the urine fingerprints allowed discrimination of the different diets. Variables were then classified according to their dependence on lipid and catechin intake (ANOVA). Nine variables were identified as catechin metabolites of tissular or microbial origin. Around 1000 variables were significantly affected by the lipid content of the diet, and 76 were fully reversed by catechin supplementation. Four variables showing an increase in urinary excretion in rats fed the high-fat diets were identified as deoxycytidine, nicotinic acid, dihydroxyquinoline and pipecolinic acid. After catechin supplementation, the excretion of nicotinic acid was fully restored to the level found in the rats fed the low-fat diet. The physiological significance of these metabolic changes is discussed.
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PMID:A liquid chromatography-quadrupole time-of-flight (LC-QTOF)-based metabolomic approach reveals new metabolic effects of catechin in rats fed high-fat diets. 1848 65

A study of prescription patterns by office-based physicians was conducted to analyse the use of lipid lowering drugs (LLD) in a Germany area of 1,768,874 inhabitants during a 1-year period. The prescription database consisted of health insurance files from a random sampling of persons (n=7490) belonging to a large statutory health insurance organization during 1993-1994. During the study period LLD were prescribed to about 2.8% of the study population. Fibrates (43.7%) were the most frequently prescribed drugs followed by HMG-CoA reductase inhibitors (29.5%) and nicotinic acid with derivatives (21.7%). The prevalence of treatment rose with increasing age peaking among 60- to 69-year-olds (7.5%). More than two-thirds of the patients were not treated continuously, receiving LLD for less than 6 months. Thus, in patients being treated with LLD, the therapy seems to be ineffective due to the short episodes of drug administration. The presence of hyperlipidaemia plus additional risk factors such as hypertension led to a higher rate of LLD prescriptions than that for hyperlipidaemia alone. Only half of the patients with a history of previous myocardial infarction and hyperlipidaemia received LLD. Furthermore, patients with hyperlipidaemia and additional risk factors such as arterial hypertension, diabetes mellitus and coronary heart disease (CHD), in whom administration of LLD has often been shown to be effective, were by far too infrequently treated with these drugs. Copyright (c) 2000 John Wiley & Sons, Ltd.
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PMID:The prescribing of lipid lowering drugs during a 1-year period: analysis of 7490 health insurance files. 1902 11

This study was undertaken on the basis of several reports in the literature that pancreatic beta cells are capable of replication/regeneration and also being afforded protection against damage induced by streptozotocin. Nicotinamide was reported to give protection against streptozotocin-induced damage in rats. In the present study, two thiazolidine-4-ones with nicotinamide substitution were administered to Swiss albino mice with streptozotocin diabetes for 15 days. Concurrently, one group received nicotinic acid. Both the test compounds reversed the hyperglycaemia diabetic mice. Damage to pancreatic islets was also reduced in these groups compared to diabetic control and nicotinic acid treated groups. Since these compounds have been earlier found have antioxidant activity, one of the possible mechanisms of action could be by reducing oxidative stress in pancreas. Further, possibly by releasing nicotinamide in vivo, the molecules could have contributed to the NAD pool in pancreas and afforded protection. It is concluded that the test compounds have potential to be developed for multiple beneficial action in conditions like metabolic syndrome.
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PMID:Antidiabetic effect through islet cell protection in streptozotocin diabetes: a preliminary assessment of two thiazolidin-4-ones in Swiss albino mice. 1903 38


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