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)

Serum cholesterol is a major risk factor for cardiovascular disease. Total cholesterol, LDL cholesterol and triglycerides are positively related to cardiovascular disease, while HDL cholesterol has an inverse relationship. Measurement of lipids is essential in individuals with established cardiovascular disease or type 2 diabetes, and may also be carried out in healthy individuals as part of cardiovascular risk assessment. Lifestyle measures are important in cardiovascular disease prevention, but the mainstay of lipid lowering therapy is appropriate use of lipid lowering drugs. Total and LDL cholesterol are the primary targets for treatment, but consideration should also be given to raising HDL cholesterol and lowering triglycerides where appropriate. Statins are the most frequently used lipid lowering agents, but there is an important place for other drugs, including ezetimibe, fibrates and nicotinic acid.
 ...
PMID:Lipids for psychiatrists - an overview. 1628 Mar 39

Prolonged-release (PR) nicotinic acid (niacin) [Niaspan] is an oral, once-daily formulation of the lipid-modifying drug designed to produce less vasodilatory flushing than crystalline immediate-release (IR) nicotinic acid and less hepatotoxicity than previous sustained-release formulations of nicotinic acid.PR nicotinic acid appears to retain the same level of efficacy as crystalline IR nicotinic acid and be better tolerated than older nicotinic acid formulations. Nicotinic acid has beneficial effects on all traditional blood lipid and lipoprotein fractions and is the most effective agent for increasing high-density lipoprotein (HDL)-cholesterol (HDL-C) and reducing lipoprotein(a). The effects of PR nicotinic acid are often additive when used in combination with HMG-CoA reductase inhibitors (statins), making it a useful addition when lipid goals are not achieved with the usual statin monotherapy or when additional correction of a specific lipid abnormality is required. PR nicotinic acid also slows atherosclerotic progression and even appears to produce regression of atherosclerosis in patients on stable statin therapy. PR nicotinic acid is a logical drug choice for treating atherogenic dyslipidaemia commonly associated with type 2 diabetes mellitus and the metabolic syndrome, and has been shown to be effective in patients with diabetes without adversely affecting glycaemic control in the majority of patients. The incidence of vasodilatory flushing with PR nicotinic acid is lower than with IR nicotinic acid and it decreases substantially over time as tolerance develops. To date, there has been no clinically significant hepatotoxicity observed with PR nicotinic acid. Therefore, once-daily PR nicotinic acid appears to maximise the potential benefits of nicotinic acid, while minimising any historical tolerability or safety concerns.
 ...
PMID:Prolonged-release nicotinic acid: a review of its use in the treatment of dyslipidaemia. 1639 85

Our understanding of the relationship between the atheroprotective activities of HDL and heterogeneity of HDL particles has advanced greatly. HDL particles are highly heterogeneous in structure, intravascular metabolism and antiatherogenic activity. In this review, we discuss new findings on the antiatherogenic properties of HDL particles. Small, dense HDL possesses potent antioxidative activity but this is compromised under conditions of atherogenic dyslipidemia. HDL functional deficiency frequently coincides with reductions in HDL-cholesterol concentration and alterations in HDL metabolism and structure. Formation of small, dense HDL particles with attenuated antiatherogenic activity can be mechanistically related to HDL enrichment in triglycerides and in serum amyloid A, depletion of cholesteryl esters, covalent modification of HDL apolipoproteins and attenuated antiatherogenic function of apolipoprotein AI. Low circulating levels of HDL cholesterol might, therefore, be associated with the defective functionality of small HDL particles of abnormal structure and composition. In common metabolic diseases, such as type 2 diabetes and metabolic syndrome, deficiency of HDL particle number and function favor accelerated atherosclerosis. Therapeutic normalization of the quantity, quality and biological activities of HDL particles thus represents a novel approach to attenuating atherosclerosis in dyslipidemic individuals with metabolic disease. Cholesteryl ester transfer protein inhibitors, nicotinic acid, reconstituted HDL and other HDL-raising agents are being investigated. Induction of selective increase in the circulating concentrations of small, dense HDL3 particles with increased antiatherogenic activity seems especially promising, particularly for therapy of atherogenic dyslipidemia.
 ...
PMID:Antiatherogenic small, dense HDL--guardian angel of the arterial wall? 1650 60

Impaired effectiveness of glucose to suppress endogenous glucose production (EGP) is an important cause of worsening hyperglycemia in type 2 diabetes. Elevated free fatty acids (FFAs) may impair glucose effectiveness via several mechanisms, including rapid changes in metabolic fluxes and/or more gradual changes in gene expression of key enzymes or other proteins. Thus, we examined the magnitude and time course of effects of FFAs on glucose effectiveness in type 2 diabetes and whether glucose effectiveness can be restored by lowering FFAs. Glucose fluxes ([3-(3)H]-glucose) were measured during 6-h pancreatic clamp studies, at euglycemia (5 mmol/l glucose, t=0-240 min), and hyperglycemia (10 mmol/l, t=240-360 min). We studied 19 poorly controlled subjects with type 2 diabetes (HbA(1c) 10.9 +/- 0.4%, age 50 +/- 3 years, BMI 30 +/- 2 kg/m(2)) on at least two occasions with saline (NA- group) or nicotinic acid (NA group) infusions for 3, 6, or 16 h (NA3h, NA6h, and NA16h groups, respectively) to lower FFAs to nondiabetic levels. As a reference group, glucose effectiveness was also assessed in 15 nondiabetic subjects. There was rapid improvement in hepatic glucose effectiveness following only 3 h of NA infusion (NA3h = 31 +/- 6% suppression of EGP with hyperglycemia vs. NA- = 8 +/- 7%; P<0.01) and complete restoration of glucose effectiveness after 6 h of NA (NA6h = 41 +/- 8% suppression of EGP; P = NS vs. nondiabetic subjects). Importantly, the loss of hepatic glucose effectiveness in type 2 diabetes is completely reversible upon correcting the increased FFA concentrations. A longer duration of FFA lowering may be required to overcome the chronic effects of increased FFAs on hepatic glucose effectiveness.
 ...
PMID:Time-dependent effects of free fatty acids on glucose effectiveness in type 2 diabetes. 1673 40

Type 2 diabetes and atherosclerotic vascular disease develop in parallel. Prospective epidemiologic studies have shown a striking communality of major risk factors for both diseases. This raises the question of a "common soil". The traits of the metabolic syndrome including dyslipidemia, visceral obesity and hypertension are predictors of type 2 diabetes as well as coronary heart disease. The same applies to the environmental factors: overnutrition, physical inertia and smoking. Visceral obesity, insulin resistance and low-grade inflammation are known as major components of the common soil for metabolic syndrome and coronary heart disease. Depending on the quality of metabolic control diabetes will accelerate the progression of atherosclerosis via unstable plaque formation. The "common soil" concept provides a paradigm for an integrated therapeutic approach. This applies to a lifestyle intervention as well as a rational use of drugs in diseases of the metabolic syndrome. The medication should consider coexisting disorders of the metabolic syndrome to use pleiotropic effects. On the other hand, side effect such as the worsening of blood glucose levels caused by beta-blockers and diuretics should be avoided. The following medication should be preferred in context of the metabolic syndrome: oral antidiabetics such as acarbose, metformin and thiazolidinediones, antihypertensives such as ACE inhibitors and ARBs (angiotensin receptor blockers) and lipid-lowering drugs such as atorvastatin, rosuvastatin, and the modern nicotinic acid derivative Niaspan, respectively. The strategy using synergies in drug treatment can reduce polypharmacy and costs and improve the patients' compliance.
 ...
PMID:[Metabolic syndrome: "common soil" for diabetes and atherosclerosis. Novel approaches to an integrated therapy]. 1677 May 62

High-density lipoproteins (HDL) possess key atheroprotective biological properties, including cellular cholesterol efflux capacity, and anti-oxidative and anti-inflammatory activities. Plasma HDL particles are highly heterogeneous in physicochemical properties, metabolism, and biological activity. Within the circulating HDL particle population, small, dense HDL particles display elevated cellular cholesterol efflux capacity, afford potent protection of atherogenic low-density lipoprotein against oxidative stress and attenuate inflammation. The antiatherogenic properties of HDL can, however be compromised in metabolic diseases associated with accelerated atherosclerosis. Indeed, metabolic syndrome and type 2 diabetes are characterized not only by elevated cardiovascular risk and by low HDL-cholesterol (HDL-C) levels but also by defective HDL function. Functional HDL deficiency is intimately associated with alterations in intravascular HDL metabolism and structure. Indeed, formation of HDL particles with attenuated antiatherogenic activity is mechanistically related to core lipid enrichment in triglycerides and cholesteryl ester depletion, altered apolipoprotein A-I (apoA-I) conformation, replacement of apoA-I by serum amyloid A, and covalent modification of HDL protein components by oxidation and glycation. Deficient HDL function and subnormal HDL-C levels may act synergistically to accelerate atherosclerosis in metabolic disease. Therapeutic normalization of attenuated antiatherogenic HDL function in terms of both particle number and quality of HDL particles is the target of innovative pharmacological approaches to HDL raising, including inhibition of cholesteryl ester transfer protein, enhanced lipidation of apoA-I with nicotinic acid and infusion of reconstituted HDL or apoA-I mimetics. A preferential increase in circulating concentrations of HDL particles possessing normalized antiatherogenic activity is therefore a promising therapeutic strategy for the treatment of common metabolic diseases featuring dyslipidemia, inflammation, and premature atherosclerosis.
 ...
PMID:Functionally defective high-density lipoprotein: a new therapeutic target at the crossroads of dyslipidemia, inflammation, and atherosclerosis. 1696 45

Elevated plasma FFA cause beta-cell lipotoxicity and impair insulin secretion in nondiabetic subjects predisposed to type 2 diabetes mellitus [T2DM; i.e., with a strong family history of T2DM (FH+)] but not in nondiabetic subjects without a family history of T2DM. To determine whether lowering plasma FFA with acipimox, an antilipolytic nicotinic acid derivative, may enhance insulin secretion, nine FH+ volunteers were admitted twice and received in random order either acipimox or placebo (double-blind) for 48 h. Plasma glucose/insulin/C-peptide concentrations were measured from 0800 to 2400. On day 3, insulin secretion rates (ISRs) were assessed during a +125 mg/dl hyperglycemic clamp. Acipimox reduced 48-h plasma FFA by 36% (P < 0.001) and increased the plasma C-peptide relative to the plasma glucose concentration or DeltaC-peptide/Deltaglucose AUC (+177%, P = 0.02), an index of improved beta-cell function. Acipimox improved insulin sensitivity (M/I) 26.1 +/- 5% (P < 0.04). First- (+19 +/- 6%, P = 0.1) and second-phase (+31 +/- 6%, P = 0.05) ISRs during the hyperglycemic clamp also improved. This was particularly evident when examined relative to the prevailing insulin resistance [1/(M/I)], as both first- and second-phase ISR markedly increased by 29 +/- 7 (P < 0.05) and 41 +/- 8% (P = 0.02). There was an inverse correlation between fasting FFA and first-phase ISR (r2 = 0.31, P < 0.02) and acute (2-4 min) glucose-induced insulin release after acipimox (r2 =0.52, P < 0.04). In this proof-of-concept study in FH+ individuals predisposed to T2DM, a 48-h reduction of plasma FFA improves day-long meal and glucose-stimulated insulin secretion. These results provide additional evidence for the important role that plasma FFA play regarding insulin secretion in FH+ subjects predisposed to T2DM.
 ...
PMID:Effects on insulin secretion and insulin action of a 48-h reduction of plasma free fatty acids with acipimox in nondiabetic subjects genetically predisposed to type 2 diabetes. 1729 78

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.
 ...
PMID:Dyslipidaemia in diabetic patients: time for a rethink. 1769 54

This review considers the treatment for combined hyperlipidaemia (CH) with a combination formulation of three drugs: a statin, nicotinic acid (NA) and aspirin--a mini-polypill. CH is a highly atherogenic dyslipidaemia manifested either as familial combined hyperlipidaemia or dyslipidaemia related to the metabolic syndrome or Type 2 diabetes mellitus. These types of dyslipidaemia are highly prevalent in the general population. Statin plus extended-release NA is a promising treatment option for the normalisation of these atherogenic lipid alterations, regression of atherosclerosis, as well as for primary or secondary prevention of cardiovascular disease (CVD) events. The addition of aspirin might prove a useful adjunct that might reduce the cutaneous side effects of NA while also acting as an antiplatelet agent in high-CVD-risk patients. However, the effective dose of aspirin may need to be at least 160 mg/day. This triple combination might improve patient compliance when compared with the three drugs administered separately.
 ...
PMID:Do we need a statin-nicotinic acid-aspirin mini-polypill to treat combined hyperlipidaemia? 1792 82

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.
 ...
PMID:[Pharmacological bases of coffee nutrients for diabetes prevention]. 1797 58


<< Previous 1 2 3 4 5 6 Next >>