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Dyslipidaemia
Kinds of Dyslipidaemia Selected AbstractsGREEN TEA EXTRACT IMPEDES DYSLIPIDAEMIA AND DEVELOPMENT OF CARDIAC DYSFUNCTION IN STREPTOZOTOCIN-DIABETIC RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2006PV Anandh Babu SUMMARY 1The efficacy of green tea extract (GTE) on serum and cardiac lipids was investigated in streptozotocin (STZ)-diabetic rats. 2Diabetes was induced in rats by a single intraperitoneal injection of STZ (60 mg/kg bodyweight). Six weeks after the induction of diabetes, GTE was administered orally for 4 weeks (300 mg/kg bodyweight daily). Bodyweight, heart weight, heart weight : bodyweight ratio, blood glucose, serum and cardiac lipids were determined in experimental rats. 3In diabetic rats, there was a significant decrease in bodyweight with an increase in heart weight : bodyweight ratio and blood glucose. Diabetic rats had significantly increased serum levels of cholesterol, triglycerides, free fatty acids and low-density lipoprotein,cholesterol (LDL-C) and decreased levels of high-density lipoprotein,cholesterol (HDL-C). In the hearts of diabetic rats, there was a significant increase in cholesterol, triglycerides and free fatty acids levels, with an increase in lipoprotein lipase activity. 4The administration of GTE to diabetic rats resulted in significant recovery in bodyweight, heart weight : bodyweight ratio and blood glucose levels. The administration of GTE reduced cholesterol, triglyceride, free fatty acid and LDL-C levels, and increased HDL-C levels, in the serum of diabetic rats. In addition, GTE decreased cholesterol, triglyceride, free fatty acids levels and lipoprotein lipase activity in the myocardium of diabetic rats. These beneficial effects of GTE are ascribed to its antihyperglycaemic and hypolipidaemic activity. In conclusion, green tea can reduce the risk of cardiovascular disease in diabetes with a significant improvement in lipid metabolism. [source] High HDL-cholesterol in women with rheumatoid arthritis on low-dose glucocorticoid therapyEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2008C. García-Gómez ABSTRACT Background, Dyslipidaemia has been described in non-treated rheumatoid arthritis (RA), and improves after therapy with disease modifying anti-rheumatic drugs or glucocorticoids; however, it has generally been perceived that glucocorticoids adversely affect lipid metabolism. The association of low dose glucocorticoid therapy with plasma lipid levels was evaluated in female RA patients. Materials and methods, A cross-sectional study was conducted in 78 female RA patients [mean age: 60 (12) years; mean disease duration: 13 (9) years]. Sixty-five (83%) were on glucocorticoid therapy [total equivalent mean prednisone dose: 5·1 (1·7) mg d,1]. Each patient was assessed through a self-reported questionnaire, structured interview and physical examination. Blood samples were obtained for routine biochemistry, lipid profile and haematological tests. Lipid profiles of RA patients who were and were not on glucocorticoid therapy were compared. Results, Clinical and laboratory features of the two groups of patients were similar, except for the Health Assessment Questionnaire and body mass index, which were significantly higher in the patients on glucocorticoid therapy. These patients had 14·7% higher serum high-density lipoprotein cholesterol (HDL-c) levels than untreated patients (P = 0·043), mainly at the expense of HDL2 subfraction, which was 24·4% higher (P < 0·039), whereas HDL3-c was only 7·4% higher (P = 0·219). Serum levels of glucose and total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL -c), very low-density lipoprotein cholesterol, apolipoproteins A-I and B were not increased in patients on glucocorticoid therapy. Conclusions, Low dose glucocorticoid therapy in RA patients is associated with an increase in HDL-c, without increasing LDL-c or triglyceride. These lipid changes may overall be considered favourable. [source] P40 Dyslipidaemia and/or its complications may worsen in patients switched from a protease inhibitor (PI)-containing to an efavirenz- containing antiretroviral (ARV) regimenHIV MEDICINE, Issue 3 2000Ej O'Moore [source] Metabolic syndrome in females with polycystic ovary syndrome and International Diabetes Federation criteriaJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 1 2008Sudhindra M. Bhattacharya Abstract Aim:, To find out the incidence of metabolic syndrome (MS) in females with polycystic ovary syndrome (PCOS) and to assess the metabolic risk factors as per the definition of International Diabetes Federation. Methods:, One hundred and seventeen females (39 adolescents and 78 adults) diagnosed with PCOS underwent assessments clinically and by appropriate laboratory tests for the evidence of MS, as per the criteria laid down by International Diabetes Federation. Results:, MS was diagnosed in 54 cases (46.2%), of which 43.6% were adolescents and 47.4% were adults (difference not statistically significant). MS in females with PCOS had significantly higher body mass index compared to those who did not have MS, irrespective of age. Abnormalities in both the lipids were more common than fasting glucose abnormalities. Conclusion:, MS was found in 46.2% of females with PCOS, with both adolescents and adults being similarly affected. Dyslipidaemia is more common than impaired fasting glucose and finding one risk factor should prompt the clinician to search for other risk factors. All females with PCOS should undergo periodic screening for MS. [source] Dyslipidaemia in type 2 diabetes: a panel discussionPRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue S2 200227 June 200, Philadelphia, Report of a Round Table Discussion held during the American Diabetes Association First page of article [source] Reduced Blood Platelet Sensitivity to Aspirin in Coronary Artery Disease: Are Dyslipidaemia and Inflammatory States Possible Factors Predisposing to Sub-optimal Platelet Response to Aspirin?BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2006Leszek Markuszewski Platelet non-responsiveness to aspirin is associated with an increased risk of serious cardiovascular events. Several environmental and hereditary factors are reportedly involved in sub-optimal acetylsalicylic acid response. Forty-five coronary artery disease patients and 45 non-coronary artery disease controls received acetylsalicylic acid at a daily dose of 75,150 mg. Controls were examined twice: on the day of entering the study and 10 days later. Urinary 11-dehydrothromboxane B2 was assessed as the marker of platelet thromboxane generation. Aggregation was studied in platelet-rich plasma using turbidimetric aggregometry with collagen and arachidonic acid. Fifty to seventy percent of coronary artery disease patients showed an extent of collagen-induced aggregation above the upper quartile of the reference range compared with 8,15% in controls (P<0.003). For arachidonic acid-activated aggregation these proportions were 45,50% in coronary artery disease versus 7% in controls (P<0.007). In coronary artery disease patients, the acetylsalicylic acid-mediated platelet inhibition positively correlated with increased triglycerides (in arachidonic acid-stimulated platelets, r=0.30, P=0.0018), total cholesterol (r=0.33, P<0.0001 in coll and arachidonic acid-activated platelets) and elevated serum C-reactive protein (CRP) (r=0.27, P=0.0024). In coronary artery disease patients urine 11-dehydrothromboxane B2 concentrations were significantly increased compared to controls after 10 day acetylsalicylic acid intake (563; 313,728 pg/mg creatinine versus 321; 246,488 pg/mg creatinine, P=0.04). The incidence of suboptimal acetylsalicylic acid response incidence was more common in patients with coronary artery disease. Acetylsalicylic acid inhibition of blood platelet reactivity and thromboxane generation was less effective in these patients. Dyslipidaemia and chronic inflammatory states may promote suboptimal acetylsalicylic acid response in coronary artery disease patients. [source] Relationship of low-density lipoprotein (LDL) particle size to thyroid function status in KoreansCLINICAL ENDOCRINOLOGY, Issue 1 2009Chul Sik Kim Summary Objective, Dyslipidaemia is a well-known manifestation of thyroid dysfunction. Recently, small low-density lipoprotein (LDL) particle size has been linked with development of cardiovascular disease. To better understand the effects of thyroid dysfunction on the development of cardiovascular disease, we examined LDL particle size and lipid profiles in subjects with different thyroid function. Methods, Included were 46 patients with overt hypothyroidism, 57 patients with subclinical hypothyroidism, 46 patients with overt hyperthyroidism, 51 patients with subclinical hyperthyroidism, and 110 age- and sex-matched healthy control subjects. We measured LDL particle size and lipid profiles in these subjects. Results, No significant differences were found in LDL particle size between the groups with different thyroid function. Serum total cholesterol and LDL-cholesterol levels were significantly higher in the cases of hypothyroidism than in the cases of hyperthyroidism and the healthy control subjects. Serum triglyceride levels were higher in subjects with overt hypothyroidism than in those with overt hyperthyroidism or healthy control subjects. Conclusions, LDL particle size, the emerging risk factor for atherosclerosis, did not appear to be significantly affected by the degree of thyroid dysfunction. Increased risk of atherosclerosis in hypothyroidism does not appear to be associated with LDL particle size, the non-traditional cardiovascular risk factor. [source] Glycaemic goals in patients with type 2 diabetes: current status, challenges and recent advancesDIABETES OBESITY & METABOLISM, Issue 6 2010K. Khunti Recommendations for the management of type 2 diabetes include rigorous control of blood glucose levels and other risk factors, such as hypertension and dyslipidaemia. In clinical practice, many patients do not reach goals for glycaemic control. Causes of failure to control blood glucose include progression of underlying pancreatic , -cell dysfunction, incomplete adherence to treatment (often because of adverse effects of weight gain and hypoglycaemia) and reluctance of clinicians to intensify therapy. There is increasing focus on strategies that offer potential to improve glycaemic control. Structured patient education has been shown to improve glycaemic control and other cardiovascular risk factors in people with type 2 diabetes. Payment of general practitioners by results has been shown to improve glycaemic control. New classes of glucose-lowering agents have expanded the treatment options available to clinicians and patients and include the dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists. These new classes of therapy and other strategies outlined above could help clinicians to individualize treatment and help a greater proportion of patients to achieve long-term control of blood glucose. [source] Colesevelam lowers glucose and lipid levels in type 2 diabetes: the clinical evidenceDIABETES OBESITY & METABOLISM, Issue 5 2010Vivian A. Fonseca Simultaneous control of blood glucose and other risk factors such as hypertension and dyslipidaemia is essential for reducing the risk of complications associated with type 2 diabetes mellitus (T2DM). As relatively few patients with T2DM have their risk factors managed to within the limits recommended by the American Diabetes Association, American College of Endocrinology or National Cholesterol Education Program Adult Treatment Panel III guidelines, treatment that can simultaneously control more than one risk factor is of therapeutic benefit. Clinical studies have shown that bile acid sequestrants have glucose-lowering effects in addition to their low-density lipoprotein cholesterol-lowering effects in patients with T2DM. The bile acid sequestrant colesevelam hydrochloride is approved as an adjunct to antidiabetes therapy for improving glycaemic control in adults with T2DM. This review examines data from three phase III clinical trials that evaluated the glucose- and lipid-lowering effects of colesevelam when added to the existing antidiabetes treatment regimen of patients with T2DM. [source] Interpreting clinical trials of diabetic dyslipidaemia: new insightsDIABETES OBESITY & METABOLISM, Issue 3 2009A. S. Wierzbicki Current treatment guidelines highlight the importance of aggressive lipid-modifying therapy in reducing cardiovascular risk in patients with type 2 diabetes. Statins are established as the cornerstone of dyslipidaemia management in diabetic patients, based on their efficacy in lowering levels of low-density lipoprotein cholesterol (LDL-C). However, statins fail to address the high residual cardiovascular risk in treated patients, some of which may be attributable to low HDL cholesterol (HDL-C) and elevated triglycerides and to a preponderance of small, dense LDL particles, indicating the need for further intervention. Fibrates are effective against all components of atherogenic dyslipidaemia associated with type 2 diabetes. Clinical studies, most notably the Fenofibrate Intervention and Event Lowering in Diabetes, indicate that fibrates, most likely in combination with a statin, have a secondary role in reducing cardiovascular risk in patients with type 2 diabetes, particularly in those without prior cardiovascular disease or patients with low HDL-C. Results are awaited from the ongoing Action to Control Cardiovascular Risk in Diabetes trial to fully evaluate the outcome benefits of this combination strategy. [source] Novel pathways for glycaemic control in type 2 diabetes: focus on bile acid modulationDIABETES OBESITY & METABOLISM, Issue 11 2008Eliot A. Brinton Type 2 diabetes is a common disorder with high risk of macrovascular and microvascular complications. These complications are largely driven by hyperglycaemia, dyslipidaemia and hypertension, for which aggressive treatment is thus warranted. Achieving and maintaining control of all three risk factors is especially difficult, however, and new therapeutic approaches could be useful. Bile acids have a well-established and important role in cholesterol homeostasis. Normally, their levels are maintained primarily by ileal reabsorption and enterohepatic recycling. Bile acid sequestrants bind bile acids in the intestine, reduce this recycling and deplete the bile acid pool, thereby stimulating use of hepatic cholesterol for bile acid synthesis, which leads to accelerated removal of LDL from the plasma and a decrease in LDL-cholesterol levels. Interestingly, recent evidence suggests that bile acid sequestrants can lower glucose levels to a clinically meaningful degree. This review presents this evidence and the possible mechanisms by which these glucose-lowering effects occur and discusses the apparently unique ability of bile acid sequestrants among lipid-lowering agents to significantly improve two cardiovascular risk factors, hyperglycaemia and dyslipidaemia. There is renewed interest in the use of bile acid sequestrants in individuals with type 2 diabetes, most of whom would benefit from additional reductions in both LDL-cholesterol and glycaemia. [source] Pomegranate flower: a unique traditional antidiabetic medicine with dual PPAR-,/-, activator propertiesDIABETES OBESITY & METABOLISM, Issue 1 2008Yuhao Li PPARs are transcription factors belonging to the superfamily of nuclear receptors. PPAR-, is involved in the regulation of fatty acid (FA) uptake and oxidation, inflammation and vascular function, while PPAR-, participates in FA uptake and storage, glucose homeostasis and inflammation. The PPARs are thus major regulators of lipid and glucose metabolism. Synthetic PPAR-, or PPAR-, agonists have been widely used in the treatment of dyslipidaemia, hyperglycaemia and their complications. However, they are associated with an incidence of adverse events. Given the favourable metabolic effects of both PPAR-, and PPAR-, activators, as well as their potential to modulate vascular disease, combined PPAR-,/-, activation has recently emerged as a promising concept, leading to the development of mixed PPAR-,/-, activators. However, some major side effects associated with the synthetic dual activators have been reported. It is unclear whether this is a specific effect of the particular synthetic compounds or a class effect. To date, a medication that may combine the beneficial metabolic effects of PPAR-, and PPAR-, activation with fewer undesirable side effects has not been successfully developed. Pomegranate plant parts are used traditionally for the treatment of various disorders. However, only pomegranate flower has been prescribed in Unani and Ayurvedic medicines for the treatment of diabetes. This review provides a new understanding of the dual PPAR-,/-, activator properties of pomegranate flower in the potential treatment of diabetes and its associated complications. [source] Screening and diagnosis of prediabetes: where are we headed?DIABETES OBESITY & METABOLISM, Issue 2007K. G. M. M. Alberti It is currently estimated that more than 300 million people have impaired glucose tolerance (IGT), putting them at increased risk for type 2 diabetes mellitus (T2DM) and its adverse consequences. In addition, many others are at risk on the basis of a family history of T2DM, obesity, dyslipidaemia and hypertension. Screening for risk should include both blood glucose testing in high-risk populations and prescreening (e.g. by questionnaire, waist circumference measurement) to identify high-risk individuals in overall low-risk populations; these individuals should then undergo glucose testing. Fasting plasma glucose measurement cannot diagnose IGT; the preferred definite test for diagnosis is oral glucose tolerance testing. [source] Cardiovascular metabolic syndrome , an interplay of, obesity, inflammation, diabetes and coronary heart diseaseDIABETES OBESITY & METABOLISM, Issue 3 2007J. S. Rana Cardiovascular disease is currently one of the biggest causes of morbidity and mortality facing humanity. Such a paradigm shift of disease pattern over the last century has only worsened due to the alarming global prevalence of obesity and type 2 diabetes. In recent years there is increasing focus on inflammation as one of the key players in the patho-physiology of these disorders. In addition to these overt risk factors new research is unraveling the significance of a constellation of early metabolic abnormalities that include weight gain, insulin resistance, prehypertension and a specific pattern of dyslipidaemia. There exists a complex interrelationship of these various metabolic disorders and their effect on cardiovascular system. Simplified explanation can be that inflammation increases insulin resistance, which in turn leads to obesity while perpetuating diabetes, high blood pressure, prothrombotic state and dyslipidaemia. While inflammation and insulin resistance have direct adverse effects on cardiac muscle, these metabolic abnormalities as a whole cause causes cardiovascular complications; warranting a multi pronged therapeutic and preventive approach for the ,Cardiovascular Metabolic Syndrome' as an entity. [source] The metabolic syndrome: evolving evidence that thiazolidinediones provide rational therapyDIABETES OBESITY & METABOLISM, Issue 4 2006Kathleen L. Wyne The metabolic syndrome, also known as the dysmetabolic syndrome, syndrome X or the insulin resistance syndrome, refers to the clustering of cardiovascular disease risk factors that are present in many individuals who are at increased risk for both cardiovascular events and type 2 diabetes. Prediabetic subjects typically exhibit an atherogenic pattern of cardiovascular risks that is associated with hyperinsulinaemia. Thus, identification of components of the metabolic syndrome is important if patients are to be treated early enough to prevent cardiovascular events and other complications related to diabetes. Therapies targeted to specific components of the metabolic syndrome such as improving glycaemic control, managing dyslipidaemia and reducing the prothrombotic state should help to minimize cardiovascular risk, particularly if initiated early. Traditional pharmacologic agents used to manage the individual components of the metabolic syndrome do not typically impact the other components. The thiazolidinediones, a new class of agents that improve insulin resistance, have the ability, in addition to their glucose-lowering effects, to exert several powerful anti-atherogenic properties, including anti-inflammatory effects in the vascular endothelium, redistribution of visceral fat and reduction of insulin resistance, hyperinsulinaemia and hyperproinsulinaemia. This makes the thiazolidinediones ideal candidates for the early treatment of many components associated with the metabolic syndrome. [source] Insulin resistance , a common link between type 2 diabetes and cardiovascular diseaseDIABETES OBESITY & METABOLISM, Issue 3 2006Harold E. Lebovitz Evidence suggests that diabetes and cardiovascular disease (CVD) may share an underlying cause(s), a theory known as the ,common soil' hypothesis. Insulin resistance is central both to the progression from normal glucose tolerance to type 2 diabetes and to a constellation of cardiovascular risk factors known as the metabolic syndrome. These risk factors include visceral obesity and dyslipidaemia characterized by low levels of high-density lipoprotein cholesterol, hypertriglyceridaemia and raised small dense low-density lipoprotein particle levels. Changes in adipose tissue mass and metabolism may link insulin resistance and visceral obesity, a condition that is common in type 2 diabetes. Furthermore, weight reduction, increased physical activity, metformin and acarbose have been shown to reduce the development of type 2 diabetes in genetically predisposed subjects and may decrease the high cardiovascular risk of patients with diabetes. Some fatty acid derivatives can affect energy metabolism by activating peroxisome proliferator-activated receptors (PPARs), nuclear receptors that play a key role in energy homeostasis. These receptors represent an ideal therapeutic target for reducing cardiovascular risk, because they are involved in the regulation of both insulin action and lipid metabolism. In addition to lifestyle changes, PPAR, agonists such as thiazolidinediones are frequently beneficial and have been shown to ameliorate insulin resistance, while activation of PPAR, (e.g. by fibrates) can lead to improvements in free fatty acid oxidation and lipid profile, and a reduction in cardiovascular events. The development of agents with both PPAR, and PPAR, activity promises added benefits with amelioration of insulin resistance, delayed progression to and of type 2 diabetes and a reduction of CVD. [source] The effects of lipid-lowering drug therapy on cardiovascular responsiveness in type 2 diabetic patientsDIABETES OBESITY & METABOLISM, Issue 1 2006Laurence Guy HowesArticle first published online: 18 MAR 200 Type 2 diabetes is associated with a high prevalence of dyslipidaemia and a high incidence of cardiovascular disease. Lipid lowering therapy with HMG Co-A reductase inhibitors (statins) reduce the risk of cardiovascular events in type 2 diabetic and non-diabetic patients, effects which are believed to be partly due to improvements in vascular function. The aetiology of abnormal vascular function in type 2 diabetics is likely to be multifactorial and the pattern of vascular dysfunction in type 2 diabetes may differ from that which occurs in non-diabetic patients with dyslipidaemia. Abnormalities in endothelium derived hyperpolarising factor (EDHF) mediated vasodilation in resistance vessels may be more prominent in both type 1 and type 2 diabetes than in non-diabetic patients with endothelial dysfunction. The effects of lipid lowering therapy on vascular responsiveness may differ in type 2 diabetic patients from those found in non-diabetic patients. Statin therapy does not appear to improve responses to endothelial dependent vasodilators in type 2 diabetics, but may alter the ratio between nitric oxide (NO) and EDHF mediated responses. Fibrate therapy improves flow mediated dilation of brachial arteries in type 2 diabetic patients, but only appears to improve endothelium dependant vasodilator responses in resistance vessels when given in conjunction with co-enzyme Q. [source] Insulin resistance, diabetes and cardiovascular risk: approaches to treatmentDIABETES OBESITY & METABOLISM, Issue 6 2005Daniel E. Rosenberg Abstract:, The prevalence of diabetes is increasing worldwide. Insulin resistance and diabetes mellitus are major predictors of cardiovascular ischaemic disease. Other risk factors for cardiovascular death including hypertension, dyslipidaemia, smoking and visceral obesity are especially lethal in diabetics. C-reactive protein, plasminogen activator inhibitor-1, matrix metalloproteinases and other emerging risk factors and their roles are continually being researched and discovered. Treatment of this syndrome must be aimed at lifestyle modification, glycaemic control and management of concomitant risk factors. Diet and exercise play a vital role in the treatment of diabetes and the metabolic syndrome. Weight reduction and increased physical activity will improve insulin resistance, hyperglycaemia, hypertension and dyslipidaemia. Hypertension management has been shown to be especially important in diabetics to prevent cardiovascular events. Likewise, multiple clinical trials show that reduction of cholesterol is even more vital in diabetics than the general population for risk reduction of coronary disease. There is a great deal of evidence that tight control of glycaemia is essential to treatment of this condition. There are a variety of available pharmacological agents available including metformin, insulin secretagogues, alpha-glucosidase inhibitors, thiazolidinediones and insulin. The mechanisms and side effects of these medications are discussed. As macrovascular disease is the major cause of morbidity and mortality, an early, aggressive, multi-factorial approach to treatment of the metabolic syndrome and diabetes is vital to prevent adverse cardiac outcomes. [source] Metabolic, endocrine and haemodynamic risk factors in the patient with peripheral arterial diseaseDIABETES OBESITY & METABOLISM, Issue 2002Jill J. F. Belch The morbidity and mortality associated with peripheral arterial disease (PAD) creates a huge burden in terms of costs both to the patient and to the health service. PAD is a deleterious and progressive condition that causes a marked increase in the risk of cardiovascular and cerebrovascular events. Further, PAD has a major negative impact on quality of life and mortality, and is associated with an increased risk of limb amputation. The clinical profile of patients at risk of PAD overlaps considerably with the known cardiovascular risk factors. These include, increasing age, smoking habit, diabetes, hypertension, dyslipidaemia, male sex and hyperhomocysteinaemia. For women, hormone replacement therapy appears to be associated with a reduced risk of PAD. Published PAD guidelines recommend aggressive management of risk factors, stressing the importance of lifestyle modification, antiplatelet agents, treating dyslipidaemia and diabetes. However, a large number of patients with PAD go undetected, either because they do not report their symptoms or because they are asymptomatic. It is therefore important to improve detection rates so that these patients can receive appropriate risk factor management. [source] Therapeutic considerations for postprandial dyslipidaemiaDIABETES OBESITY & METABOLISM, Issue 3 2001John R. Burnett [source] What predicts the occurrence of the metabolic syndrome in a population-based cohort of adult healthy subjects?DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2009S. Bo Abstract Background Metabolic syndrome (MS), the concurrence of hyperglycaemia, dyslipidaemia, hypertension and visceral obesity, increases cardiovascular risk and mortality. Predictors of MS were previously evaluated in patients without the full syndrome, but with some of its traits. This might confound the resulting associations. Methods The relationship between baseline variables and MS development was evaluated in healthy middle-aged subjects without any MS component at baseline, over a 4.5-year follow-up. Results From a population-based cohort of 1658 subjects, 241 individuals showed no MS components and 201 (83.4%) of them participated in a follow-up screening. At baseline, patients who developed the MS (n = 28/201; 13.9%) showed significantly higher Homeostasis Model Assessment-Insulin Resistance score (HOMA-IR) and C-reactive protein (CRP) values, and lower exercise level than subjects who did not. In a multiple logistic regression analysis, after multiple adjustments, the only baseline variable significantly (p < 0.01) associated with the MS was CRP (OR = 4.05; 95% CI 2.23,7.38; p < 0.001). Results did not change after adjusting for weight gain. The area under the receiver-operating curve was 0.83 for CRP after multiple adjustments. The optimal cut-off point of baseline CRP values was 2.1 mg/L, with 86% (95% CI 81,90) sensitivity and 75% (69,81) specificity in predicting the MS. Baseline CRP resulted associated with after-study glucose values in a multiple regression model (, = 0.14; 0.08,0.20; p < 0.001). Conclusions Higher baseline CRP values confer a significant increased risk of developing the MS in healthy subjects, independently of weight gain. Copyright © 2009 John Wiley & Sons, Ltd. [source] Impaired glucose regulation and type 2 diabetes in children and adolescentsDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2008Kerstin Kempf Abstract Diabetes mellitus in paediatric patients used to be almost exclusively type 1, but in recent years, case series as well as hospital-based and population-based studies indicated that the number of children and adolescents with type 2 diabetes (T2DM) has been increasing. This development is alarming since T2DM in youth is usually not an isolated condition, but accompanied by other cardiovascular risk factors such as obesity, dyslipidaemia, hypertension and low-grade inflammation. In adults, numerous studies provided detailed data on prevalence, incidence and risk factors for the development of T2DM, but for children and adolescents clinical and experimental data are still rather limited. This review provides an overview about the epidemiology and pathogenesis of T2DM in youth and about impaired glucose regulation as major risk factor for diabetes development with a special focus on the recent literature on clinical and lifestyle-related risk factors. Differences in incidence and prevalence across different populations indicate that ethnic background and genetic pre-disposition may be important risk determinants. In addition, epigenetic factors and foetal programming appear to confer additional risk before birth. Among the environmental and lifestyle-related risk factors there is evidence that obesity, hypercaloric diet, physical inactivity, socio-economic position (SEP), smoking, low-grade inflammation, psychosocial stress and sleeping patterns contribute to the risk for T2DM. However, the assessment of the relevance of risk factors and of incidence or prevalence estimates in youth is complicated by methodological issues that are also discussed. Copyright © 2008 John Wiley & Sons, Ltd. [source] Lipid-lowering therapy in patients with type 2 diabetes: the case for early interventionDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2008Armin Steinmetz Abstract Chronic complications of type 2 diabetes, in particular, macrovascular complications, confer substantial morbidity and mortality and adversely affect a patient's quality of life. Early intensive intervention to control cardiovascular risk factors is essential in clinical management. Atherogenic dyslipidaemia characterized by elevated triglycerides, a low level of high-density lipoprotein cholesterol (HDL-C), and an increase in the preponderance of small, dense low-density lipoprotein (LDL) particles, is a key modifiable risk factor for macrovascular diabetic complications. Lowering low-density lipoprotein cholesterol (LDL-C) with a statin (or the combination of statin and ezetimibe) is the main focus for reducing cardiovascular risk in patients with diabetes. However, statins fail to address the residual cardiovascular risk associated with low HDL-C. Fibrates are effective against all components of the atherogenic dyslipidaemia associated with type 2 diabetes. Secondary analyses of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study suggest a role for early treatment with fenofibrate in improving cardiovascular risk reduction in type 2 diabetes and provide safety data supporting the use of fenofibrate in combination with a statin. Data from the FIELD study suggest that fenofibrate may also have potential to impact on microvascular diabetic complications associated with type 2 diabetes. Data are awaited from the ongoing Action to Control Cardiovascular Risk in Diabetes (ACCORD) study to evaluate the outcome benefits of combining fenofibrate with a statin in patients with type 2 diabetes. Finally, in view of divergent study results and outstanding data, assessment of the risk of the individual with type 2 diabetes is mandatory to assist clinical decision-making when initiating lipid therapy. Copyright © 2008 John Wiley & Sons, Ltd. [source] CB1 receptors: emerging evidence for central and peripheral mechanisms that regulate energy balance, metabolism, and cardiovascular healthDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 7 2007Daniela Cota Abstract Insulin resistance, dyslipidaemia and obesity are the major cardiometabolic risk factors contributing to the development of type 2 diabetes and cardiovascular disease (CVD). Owing to the increasing prevalence of obesity, type 2 diabetes, and CVD, new and effective pharmacologic therapies are urgently needed. In this regard, the endogenous cannabinoid system (ECS), a neuromodulatory system involved in the regulation of various aspects of energy balance and eating behaviour through central and peripheral mechanisms, may present the potential to meet this need. In the central nervous system (CNS), cannabinoid type 1 (CB1) receptors and their respective ligands, the endocannabinoids, have a significant role in the modulation of food intake and motivation to consume palatable food. CB1 receptors have also been found in organs involved in the regulation of metabolic homeostasis, such as liver, white adipose tissue, muscle and pancreas. Dysregulation of the ECS has been associated with the development of dyslipidaemia, glucose intolerance, and obesity, and CB1 receptor blockade may have a role in ameliorating these metabolic abnormalities. Thus, pharmacologic options targeting the ECS may provide a novel, effective approach to the prevention and management of CVD, type 2 diabetes and obesity. Copyright © 2007 John Wiley & Sons, Ltd. [source] The different mechanisms of insulin sensitizers to prevent type 2 diabetes in OLETF ratsDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2007Sung Hee Choi Abstract Objective To investigate the effects of pioglitazone and metformin treatment during pre-diabetic period for the prevention of diabetes in a rat model. Methods OLETF rats aged 18-weeks, were treated with pioglitazone (10 mg/kg/day) and metformin (300 mg/kg/day) for 10 weeks from their pre-diabetic period. We measured weight, lipid profiles, fat distribution, glucose tolerance, and pancreatic insulin content. Results Prominent weight gain (mostly subcutaneous fat area) was observed in the pioglitazone-treated OLETF (O-P) rats versus significant weight loss was observed in the metformin-treated OLETF (O-M) rats. Pioglitazone reversed the serum triglyceride (TG) and FFAs levels to normal (TG 0.46 ± 0.04 vs 0.88 ± 0.05 mmol/l in LETO). At the age of 28 weeks, the O-P rats showed completely normal glucose tolerance, and the glucose disposal rate (GDR) was markedly improved (25.6 ± 0.4 vs 20.6 ± 0.5 mg/min/kg in O-C, p < 0.05). The O-M rats also showed an improved fasting glucose and GDR level, but not as much as those with O-P rats. The pancreas insulin contents were much improved in the O-P rats (22.9 ± 1.2 vs 18.8 ± 1.3 nmol/pancreas in O-M rats, p < 0.05) with histological improvement. Conclusion The pre-diabetic treatment with pioglitazone, despite significant weight gain, completely prevents to develop diabetes and enhances beta cell function with preservation of islet cell changes. Metformin treatment was also effective, but mainly by ameliorating the insulin resistance with marked reduction in body weight. The reversal of dyslipidaemia and the fat redistribution might contribute to the greater improvement of pioglitazone treatment compared to metformin in OLETF rats. Copyright © 2007 John Wiley & Sons, Ltd. [source] Insulin resistance in type 2 diabetes: role of fatty acids,DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S2 2002Peter Arner Abstract Insulin resistance is one of the key factors responsible for hyperglycaemia in type 2 diabetes and can result in a number of metabolic abnormalities associated with cardiovascular disease (insulin resistance syndrome), even in the absence of overt diabetes. The mechanisms involved in the development of insulin resistance are multifactorial and are only partly understood, but increased availability of free fatty acids (FFAs) is of particular importance for the liver and skeletal muscle. The role of FFAs in type 2 diabetes is most evident in obese patients who have several abnormalities in FFA metabolism. Because of a mass effect, the release of FFAs from the total adipose tissue depot to the blood stream is increased and the high concentration of circulating FFAs impairs muscle uptake of glucose by competitive inhibition. In upper-body obesity, which predisposes individuals to type 2 diabetes, the rate of lipolysis is accelerated in visceral adipose tissue. This results in a selective increase in FFA mobilisation to the portal vein, which connects visceral fat to the liver. A high ,portal' FFA concentration has undesirable effects on the liver, resulting in dyslipidaemia, hyperinsulinaemia, hyperglycaemia and hepatic insulin resistance. Recently, a new class of antidiabetic agents, the thiazolidinediones (TZDs) or ,glitazones' has been developed. A prominent effect of these agents is the lowering of circulating FFA levels and it is believed, but not yet proven, that this interaction with FFAs constitutes a major mechanism behind the glucose-lowering effect of the TZDs. Copyright © 2002 John Wiley & Sons, Ltd. [source] Peripheral arterial disease in diabetes,a reviewDIABETIC MEDICINE, Issue 1 2010E. B. Jude Diabet. Med. 27, 4,14 (2010) Abstract Diabetic patients are at high risk for peripheral arterial disease (PAD) characterized by symptoms of intermittent claudication or critical limb ischaemia. Given the inconsistencies of clinical findings in the diagnosis of PAD in the diabetic patient, measurement of ankle-brachial pressure index (ABI) has emerged as the relatively simple, non-invasive and inexpensive diagnostic tool of choice. An ABI < 0.9 is not only diagnostic of PAD even in the asymptomatic patient, but is also an independent marker of increased morbidity and mortality from cardiovascular diseases. With better understanding of the process of atherosclerosis, avenues for treatment have increased. Modification of lifestyle and effective management of the established risk factors such as smoking, dyslipidaemia, hyperglycaemia and hypertension retard the progression of the disease and reduce cardiovascular events in these patients. Newer risk factors such as insulin resistance, hyperfibrinogenaemia, hyperhomocysteinaemia and low-grade inflammation have been identified, but the advantages of modifying them in patients with PAD are yet to be proven. Therapeutic angiogenesis, on the other hand, represents a promising therapeutic adjunct in the management of PAD in these patients. Outcomes after revascularization procedures, such as percutaneous transluminal angioplasty and surgical bypasses in diabetic patients, are poorer, with increased perioperative morbidity and mortality compared with that in non-diabetic patients. Amputation rates are higher due to the distal nature of the disease. Efforts towards increasing awareness and intensive treatment of the risk factors will help to reduce morbidity and mortality in diabetic patients with PAD. [source] Effect of ABCA1 variant on atherogenic dyslipidaemia in patients with Type 2 diabetes treated with rosiglitazoneDIABETIC MEDICINE, Issue 6 2009S. E. Park Abstract Aims, To investigate the effect of two common ATP-binding cassette transporter 1 (ABCA1) polymorphisms (rs4149263 and rs2020927) on atherogenic dyslipidaemia in Korean Type 2 diabetic patients who were treated with rosiglitazone. Patients and methods, Two hundred and fifty-six patients with Type 2 diabetes who had never previously received peroxisome proliferator-activated receptor gamma (PPAR-,) agonists or lipid-lowering treatment were treated with 4 mg of rosiglitazone daily for 12 weeks without any adjustment to their glucose-lowering regimen. The primary outcome was the change in atherogenic index of plasma (AIP), calculated as log [triglyceride (mmol/l)/high-density lipoprotein cholesterol (mmol/l)], before and after rosiglitazone treatment. The effect of rosiglitazone on the change in AIP was compared across the ABCA1 single nucleotide polymorphisms (SNPs) rs41429263 and rs2020927. Results, Before adjustment, the change in AIP at 12 weeks was significantly different across the rs4149263 genotypes [median (interquartile range): ,0.05 (,0.21, 0.09) for TT; 0.02 (,0.09, 0.17) for TC; and 0.11 (0.03, 0.25) for CC; P = 0.003], but not across the rs2020927 [,0.04 (,0.18, 0.10) for TT; 0.03 (,0.17, 0.15) for TC; and ,0.03 (,0.13, 0.10) for CC; P = 0.401]. After controlling for age, gender and duration of diabetes, the presence of the C-allele was significantly associated with an increase in AIP by 0.13 [95% confidence interval (CI), 0.04,0.21; P = 0.003]. This association did not change significantly when body mass index and pretreatment metabolic parameters were additionally controlled for (the change in AIP: 0.14; 95% CI, 0.04,0.24; P = 0.007). Conclusions, The ABCA1 SNP rs4149263 may be associated with the change in atherogenic lipid profile in Type 2 diabetes treated with rosiglitazone. [source] Plasma triglycerides and LDL cholesterol are related in a parabolic fashion in the general population and patients with Type 2 diabetes mellitus: long-term follow-up results from the Hoorn studyDIABETIC MEDICINE, Issue 9 2008M. C. G. J. Brouwers Abstract Aims Low-density lipoprotein cholesterol (LDL-C) levels are often fairly normal in Type 2 diabetes mellitus (DM). We anticipated that a parabolic relation between plasma triglycerides and LDL-C, as previously demonstrated in familial combined hyperlipidaemia (FCHL), might account for this phenomenon. Methods Our hypothesis was tested in 1343 subjects derived from the general population who were studied on two occasions 6 years apart (the Hoorn study). Three groups were constructed depending on plasma triglycerides: group A (individuals with both measurements below 1.5 mmol/l), group B (one measurement below and one above 1.5 mmol/l) and group C (both measurements above 1.5 mmol/l). Diabetes status was ascertained by an oral glucose tolerance test. Results In a mixed linear model, a significant, positive relation between triglycerides and LDL-C was observed for males in group A (,a = 0.5, P < 0.001) and group B (,b = 0.2, P < 0.001), whereas a significant negative relation was found for males in group C (,c = ,0.2, P = 0.003). The regression slopes did not differ between diabetic and non-diabetic subjects. Similar results were obtained for women, with the exception that the relation was not significantly negative in group C (,c = ,0.1, P = 0.4). Conclusion Plasma triglcyerides and LDL-C are related in a parabolic fashion, not only in FCHL, but also in the general population and Type 2 DM. These findings aid our interpretation of typical dyslipidaemia and the effects of treatment that are frequently observed in hypertriglyceridaemic states. [source] The islet autoantibody titres: their clinical relevance in latent autoimmune diabetes in adults (LADA) and the classification of diabetes mellitusDIABETIC MEDICINE, Issue 2 2008A. W. Van Deutekom Abstract Latent autoimmune diabetes in the adult (LADA) is a slowly progressive form of autoimmune diabetes, characterized by diabetes-associated autoantibody positivity. A recent hypothesis proposes that LADA consists of a heterogeneous population, wherein several subgroups can be identified based on their autoimmune status. A systematic review of the literature was carried out to appraise whether the clinical characteristics of LADA patients correlate with the titre and numbers of diabetes-associated autoantibodies. We found that the simultaneous presence of multiple autoantibodies and/or a high-titre anti-glutamic acid decarboxylase (GAD),compared with single and low-titre autoantibody,is associated with an early age of onset, low fasting C-peptide values as a marker of reduced pancreatic B-cell function, a high predictive value for future insulin requirement, the presence of other autoimmune disorders, a low prevalence of markers of the metabolic syndrome including high body mass index, hypertension and dyslipidaemia, and a high prevalence of the genotype known to increase the risk of Type 1 diabetes. We propose a more continuous classification of diabetes mellitus, based on the finding that the clinical characteristics gradually change from classic Type 1 diabetes to LADA and finally to Type 2 diabetes. Future studies should focus on determining optimal cut-off points of anti-GAD for differentiating clinically relevant diabetes mellitus subgroups. [source] | ||||||||||||||||||||||||||||||||||