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Abnormal Lipid Metabolism In Diabetes

Confirmation Of The Abnormal Lipid Metabolism As A Risk Factor For The Disease Of Leukoaraiosis - Sciencedirect

Confirmation Of The Abnormal Lipid Metabolism As A Risk Factor For The Disease Of Leukoaraiosis - Sciencedirect

Volume 24, Issue 3 , March 2017, Pages 508-513 Open Access funded by King Saud University Our purpose is to screen out medical history indicators and test indicators linked to lipid metabolism which is closely correlated to leukoaraiosis (LA), and to build assistant diagnosis model based on support vector machine (SVM), which provided theoretical evidence for genesis and development of LA. One thousand LA patients who underwent magnetic resonance imaging (MRI) examination in Imaging Department was retrospectively analyzed and divided into LA group and non-LA group in accordance with examination results. Detailed clinical statistics of the two groups were collected, including test indicators related to lipid metabolism, such as total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), medical history indicators, age, sex, diabetes, hypertension, hyperlipidemia, history of intracranial infection, history of cerebral hemorrhage, cerebral infarction, lacunar infarction and relevant biochemical indexes. The study shows that patients incidence of LA was 31.10%; in accordance with Logistic analysis, the incidence of LA is significantly correlated to factors like age, hypertension, history of cerebral hemorrhage, cerebral infarction, lacunar infarction and triglyceride elevation; two SVMs, one including all variables and the other containing all screened variables were successfully established, and the formers accuracy, specificity and sensitivity respectively were 85.0%, 85.0% and 85.0% while the latters 90.0%, 100.0% and 80.0%. Test indicators and medical history indicators of lipid metabolism correlated to LA were screened out successfully. Meanwhile, an effective SVM model also was built successfully, which is able to predict Continue reading >>

Lipids And Lipoproteins In Patients With Type 2 Diabetes

Lipids And Lipoproteins In Patients With Type 2 Diabetes

Insulin resistance and type 2 diabetes are associated with a clustering of interrelated plasma lipid and lipoprotein abnormalities, which include reduced HDL cholesterol, a predominance of small dense LDL particles, and elevated triglyceride levels. Each of these dyslipidemic features is associated with an increased risk of cardiovascular disease. Increased hepatic secretion of large triglyceride-rich VLDL and impaired clearance of VLDL appears to be of central importance in the pathophysiology of this dyslipidemia. Small dense LDL particles arise from the intravascular processing of specific larger VLDL precursors. Typically, reduced plasma HDL levels in type 2 diabetes are manifest as reductions in the HDL2b subspecies and relative or absolute increases in smaller denser HDL3b and HDL3c. Although behavioral interventions such as diet and exercise can improve diabetic dyslipidemia, for most patients, pharmacological therapy is needed to reach treatment goals. There are several classes of medications that can be used to treat lipid and lipoprotein abnormalities associated with insulin resistance and type 2 diabetes, including statins, fibrates, niacin, and thiazolidinediones. Clinical trials have shown significant improvement in coronary artery disease after diabetic dyslipidemia treatment. Type 2 diabetes is associated with a cluster of interrelated plasma lipid and lipoprotein abnormalities, including reduced HDL cholesterol, a predominance of small dense LDL particles, and elevated triglycerides (1). These abnormalities occur in many patients despite normal LDL cholesterol levels. These changes are also a feature of the insulin resistance syndrome (also known as the metabolic syndrome), which underlies many cases of type 2 diabetes. In fact, pre-diabetic individuals Continue reading >>

Abnormal Lipid Metabolism | Diabetic Mediterranean Diet

Abnormal Lipid Metabolism | Diabetic Mediterranean Diet

An up-and-coming theory to explain type 2 diabetes suggests that abnormal lipid metabolism, not glucose/sugar metabolism, is the primary metabolic defect. Roger H. Unger, M.D., wrote about this in the March 12, 2008, issue of the Journal of the American Medical Association. Early in the writing of this blog entry, I realized it is much too technical formost of myreaders. If you are not interested in physiology, youcan quit reading now. Its OK . .. really. This may be the most boring blog post of mine you have ever read. Imwriting this to solidify my own understanding ofa newtheory. I assure you my prose in The Advanced Mediterranean Diet weight-loss book is not nearly this technical. Still with me? [Get out now while youre still awake!] Diabetes is defined by high blood glucose (sugar) levels. The lipid family includes triglycerides (fats and oils), sterols (e.g., cholesterol), and phospholipids (e.g., lecithin, a major cell membrane component). Fats are almost entirely composed of trigylcerides. When fats are broken down, fatty acids are produced. On the other hand, fatty acids can be joined together, along with glycerol, to form triglycerides. Glycogen is a storage form of glucose in liver and muscle tissue. In olden days,some called it animal starch. Insulinis a protein hormoneproduced by pancreatic beta cells. Insulin hasmultiple actions, not just blood sugar lowering: lowersblood glucose levels by driving glucose into cells inhibits breakdown of glycogen into glucose inhibits formation of new glucose molecules by the body promotes storage of triglycerides in fat cells (i.e., lipogenesis, fat accumulation) promotes formation of fatty acids (triglyceride building blocks) by the liver inhibits breakdown of stored triglycerides Fatty acids in muscle tissue block the u Continue reading >>

[disorders Of Lipid Metabolism In Diabetes Mellitus].

[disorders Of Lipid Metabolism In Diabetes Mellitus].

[Disorders of lipid metabolism in diabetes mellitus]. II. Medizinischen Abteilung, Allgemeinen Krankenhauses der Stadt Linz. Diabetes mellitus is the most frequent endogenous cause of fat metabolism-disorder. In diabetics the risk for arteriosclerosis is significantly higher and the clinical significance of hyperlipidemia should be estimated more serious as in non-diabetics. The predominant abnormality of fat metabolism in diabetes is hypertriglyceridemia due to an increase of triglyceride-carrying lipoproteins, the chylomicrons and the very-low-density lipoproteins. In type I-diabetics the decisive pathogenetic factor for hypertriglyceridemia is the impaired degradation of VLDL and the reduced chylomicron-clearance, caused by decreased activity of the lipoproteinlipase. In ketoacidosis there is an additional increase in hepatic VLDL-triglyceride-production due to increased lipolysis with elevated free-fatty-acid flux. Total cholesterol in type I-diabetics is only significantly elevated when metabolic control is poor, low-density lipoprotein (LDL-)-cholesterol-levels can be increased and high-density lipoprotein (HDL-)cholesterol decreased in dependence on the metabolic control. In type II-diabetics the decisive pathogenetic factor for hypertriglyceridemia is increased VLDL-triglyceride-synthesis in the liver especially due to augmented free-fatty-acid flux. Additionally the activity of the lipoproteinlipase can be reduced. Usually in non-insulin-dependent diabetics LDL-cholesterol-levels can be seen elevated and HDL-cholesterol-concentration decreased in correlation with the metabolic control. Primary hyperlipoproteinemia appears frequently in diabetics, but this can be explained by the association with obesity in type II-diabetics. Continue reading >>

Lipid Disorders In Type 1 Diabetes

Lipid Disorders In Type 1 Diabetes

1. Introduction Cardiovascular disease is the major cause of death in persons with type 1 diabetes (Libby et al., 2005). Dyslipidemia has been shown to be a significant coronary heart disease risk factor in type 1 diabetes (Soedamah-Muthu et al., 2004; Grauslund et al., 2010). Thus, it seems important to pay attention to lipid abnormalities, in patients with type 1 diabetes, in order to reduce cardiovascular disease in this population. Patients with type 1 diabetes show lipid disorders, mostly qualitative abnormalities of lipoproteins, which may promote atherogenesis. The pathophysiology of these lipid abnormalities is not totally explained, but hyperglycemia and peripheral hyperinsulinemia, due to the subcutaneous route of insulin administration, are likely to play a role. After a brief review of lipoprotein metabolism and some information on the role of insulin on lipid metabolism, quantitative abnormalities then qualitative abnormalities of lipoproteins, in type 1 diabetes, will be discussed. 2. Brief review of lipoprotein metabolism Lipoproteins, which transport non-water soluble cholesterol and triglycerides in plasma, are spherical particles composed of a central core of non-polar lipids (cholesterol esters, triglycerides) and a surface monolayer of phospholipids, free cholesterol and apolipoproteins. Lipoproteins are generally classified according to their density as chylomicron, Very Low Density Lipoprotein (VLDL), Intermediate Density Lipoprotein (IDL), Low Density Lipoprotein (LDL) and High Density Lipoprotein (HDL). An overview of lipoprotein metabolism is shown in Figure 1. 2.1. Chylomicrons Chylomicrons, the largest lipoprotein particles, are responsible for the transport of dietary triglycerides and cholesterol. Chylomicrons are composed of triglycerides ( Continue reading >>

Lipid Disorders In Type 1 Diabetes - Em|consulte

Lipid Disorders In Type 1 Diabetes - Em|consulte

Received:24April2009; accepted:29April2009 Anomalies lipidiques au cours du diabte de type 1 Service dendocrinologie, de diabtologie et des maladies mtaboliques, hpital du Bocage, 2, boulevard Marchal-de-Lattre-de-Tassigny, 21000 Dijon, France Patients with type 1 diabetes (T1D) also present with lipid disorders. Quantitative abnormalities of lipoproteins are observed in T1D patients with poor glycaemic control (increased plasma triglycerides and low-density lipoprotein [LDL] cholesterol) or nephropathy (increased triglycerides and LDL cholesterol, low level of high density lipoprotein [HDL] cholesterol). In cases of T1D with optimal glycaemic control, plasma triglycerides and LDL cholesterol are normal or slightly decreased, while HDL cholesterol is normal or slightly increased. Several qualitative abnormalities of lipoproteins, which are potentially atherogenic, are observed in patients with T1D, even in those with good metabolic control. These abnormalities include increased cholesterol-to-triglyceride ratios within very low-density lipoprotein (VLDLs), increased triglycerides in LDLs and HDLs, compositional changes in the peripheral layer of lipoproteins, glycation of apolipoproteins, increased oxidation of LDLs and an increase in small, dense LDL particles. These qualitative changes in lipoproteins are likely to impair their function. In vitro , VLDLs and LDLs from patients with T1D induced abnormal responses in the cellular cholesterol metabolism of human macrophages. HDLs from patients with T1D are thought to be less effective in promoting cholesterol efflux from cells, and have been shown to have reduced antioxidative and vasorelaxant properties. These qualitative abnormalities are not fully explained by hyperglycaemia and may be partly due to peripheral hyperi Continue reading >>

Estimation Of Biochemical Parameters Of Lipid Metabolism In Diabetics | Biomedical And Pharmacology Journal

Estimation Of Biochemical Parameters Of Lipid Metabolism In Diabetics | Biomedical And Pharmacology Journal

How to Citeclose |Publication Historyclose Views:(Visited 134 times, 1 visits today)PDF Downloads:116 Estimation of Biochemical Parameters of Lipid Metabolism In Diabetics Manishi Singh1, Manika Singh2 and M. P Singh3 1Department of Medical Biochemistry, Chiraiyu Medical College, Bhopal2Department of Oral Medicine and Radiology, Rishi Raj Dental College and Research Centre, Bhopal, India. Department of Conservative Dentistry, Peoples College of Dental Sciences and Research Centre, Bhopal, India. In this present study included 40 morbid and 50 healthy control all were in age group of 20 to 60 years having renal failure of various etiology but in this study group patients of diabetes with ESRD studied, male, female ratio 3:2, lipid profile, blood sugar, apolipoprotein A and B were estimated by fully automated clinical chemistry analyzer, orion diagnostic immuno chemical assay and blood sugar by GOD, POD method. It was found that patient of ESRD with diabetes had HDL-chol, APO A1, APO A1/APO B, HDL Chol./T.Chol. was significantly decreased (p <0.05) as compared to control. Same time T-Chol., TG, LDL-Chol., VLDL-Chol, APO-B, LDL-Chol/HDL-Chol., APO B/A1, significantly increased (p<0.05) as compared to control. It can be concluded from the present study that patient of ESRD with diabetes had significantly decreased level of HDL-Chol, APO A1, APO A1/ APO B, and significantly increased level of TG, VLDL, APO B/APO A1, ratio on atherogenic index was evaluated in all patient dialyzed and undialyzed in both groups. Indicated that atherogenic changes is more advanced in diabetic than in non diabetics with ESRD, this is the scope of dyslipidemia in diabetics with nephropathy is an addition to the effect of basic disease. Hyperlipidemia; Hyperglycemia; Lipid metabolism;Lipids; ESRD Continue reading >>

Lipid Metabolism | Diabetes And Obesity Center Of Excellence

Lipid Metabolism | Diabetes And Obesity Center Of Excellence

Diabetes and Obesity Center of Excellence Cardiovascular disease (CVD) is the leading cause of death in the United States. Well-known risk factors for CVD include a high blood level of low density lipoprotein (LDL), the bad form of cholesterol, and a low level of high density lipoprotein (HDL), the good form of cholesterol. Diabetes and metabolic syndrome represent other important risk factors for CVD. Indeed, CVD is the major cause of death in both type 1 and type 2 diabetes. Almost one quarter of all Americans have some form of CVD, which accounts for 30% of deaths nationwide. CVD includes the following: Atherosclerosis.Atherosclerosis is the buildup of plaque on the inner wall of an artery. It is implicated in most CVD. Stable plaque causes arteries to narrow and harden. Unstable plaque can cause blood clots, leading to heart attack, stroke and other disorders. Coronary Artery Disease (CAD).Afflicting 13 million Americans, CAD is the leading cause of CVD mortality, causing half a million U.S. deaths each year. It occurs when atherosclerosis of the coronary arteries decreases the oxygen supply to the heart, often resulting in a heart attack when cardiac muscle is deprived of oxygen. Over time, CAD can weaken the heart muscle, contributing to heart failure. Myocardial Infarction (MI). Also called a heart attack, MI occurs when the supply of blood and oxygen to an area of heart muscle is blocked, usually by a clot in a coronary artery. Each year, more than a million Americans have an MI, and almost half of those consequently die. Sudden Death.In 1/3rd of individuals with CVD, sudden death is the first manifestation of disease. Currently available tests, such as those that measure LDL and HDL levels, are weak predictors of risk for sudden death and MI. It is thus critic Continue reading >>

Diabetic Dyslipidemia: Causes And Consequences

Diabetic Dyslipidemia: Causes And Consequences

Diabetic Dyslipidemia: Causes and Consequences Division of Preventive Medicine and Nutrition, Columbia University College of Physicians and Surgeons, New York, New York 10032 Search for other works by this author on: The Journal of Clinical Endocrinology & Metabolism, Volume 86, Issue 3, 1 March 2001, Pages 965971, Ira J. Goldberg; Diabetic Dyslipidemia: Causes and Consequences, The Journal of Clinical Endocrinology & Metabolism, Volume 86, Issue 3, 1 March 2001, Pages 965971, More cardiovascular disease occurs in patients with either type 1 or 2 diabetes. The link between diabetes and atherosclerosis is, however, not completely understood. Among the metabolic abnormalities that commonly accompany diabetes are disturbances in the production and clearance of plasma lipoproteins. Moreover, development of dyslipidemia may be a harbinger of future diabetes. A characteristic pattern, termed diabetic dyslipidemia, consists of low high density lipoprotein (HDL), increased triglycerides, and postprandial lipemia. This pattern is most frequently seen in type 2 diabetes and may be a treatable risk factor for subsequent cardiovascular disease. The pathophysiological alterations in diabetes that lead to this dyslipidemia will be reviewed in this article. Causes of lipoprotein abnormalities in diabetes Defects in insulin action and hyperglycemia could lead to changes in plasma lipoproteins in patients with diabetes. Alternatively, especially in the case of type 2 diabetes, the obesity/insulin-resistant metabolic disarray that is at the root of this form of diabetes could, itself, lead to lipid abnormalities exclusive of hyperglycemia. Type 1 diabetes, previously termed insulin-dependent diabetes mellitus, provides a much clearer understanding of the relationship among diabetes, ins Continue reading >>

Association Of Insulin Resistance With Glucose And Lipid Metabolism: Ethnic Heterogeneity In Far Western China

Association Of Insulin Resistance With Glucose And Lipid Metabolism: Ethnic Heterogeneity In Far Western China

Association of Insulin Resistance with Glucose and Lipid Metabolism: Ethnic Heterogeneity in Far Western China Yi-Zhong Yan ,1 Ru-Lin Ma ,1 Jing-Yu Zhang ,1 Jia He ,1 Jiao-Long Ma ,1 Hong-Rui Pang ,1 La-Ti Mu ,1 Yu-Song Ding ,1,2 Heng Guo ,1 Mei Zhang ,1 Jia-Ming Liu ,1 Dong-Sheng Rui ,1 Kui Wang ,1and Shu-Xia Guo 1,2 1Department of Preventive Medicine, University of Shihezi, Shihezi 832000, China 2Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832000, China Received 18 August 2016; Revised 11 October 2016; Accepted 3 November 2016 Copyright 2016 Yi-Zhong Yan et al. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective. To study the relationships between IR and glucose and lipid metabolism in far western China and these relationships ethnic heterogeneity. Methods. From the baseline survey, 419 Uygur cases, 331 Kazak cases, and 220 Han cases were randomly selected, resulting in a total of 970 cases for study. FINS concentration was measured by radioimmunoassay. Results. (1) In the Kazak population, IR was correlated with hyperglycemia; high levels of TC, TG, and LDL-C; and low levels of HDL-C and abdominal obesity (all . (2) In the Uygur population, the influence of IR on hyperglycemia and abdominal obesity was the greatest. In the Kazak population, IR was associated with hyperglycemia most closely. In the Han population, IR may have had an impact on the incidence of low HDL-C levels. (3) After adjusting for sex, age, smoking status, and alcohol consumption, IR was still associated with anomalie Continue reading >>

Abnormal Lipid Metabolism In Metabolic Syndrome: An Epigenetic Perspective

Abnormal Lipid Metabolism In Metabolic Syndrome: An Epigenetic Perspective

Keywords: metabolic syndrome ; epigenetics ; dyslipidemia 1. Kraja AT, Vaidya D, Pankow JS, Goodarzi MO, Assimes TL, Kullo IJ, et al. A bivariate genome-wide approach to metabolic syndrome: STAMPEED consortium. Diabetes. 2011;60:1329-39. DOI: 10.2337/db10-1011. 2. Bruce KD, Hanson MA. The developmental origins, mechanisms, and implications of metabolic syndrome. J Nutr. 2010;140(3):648-52. DOI: 10.3945/ jn.109.111179. 3. Laker RC, Wlodek ME, Connelly JJ, Yan Z. Epigenetic origins of metabolic disease: The impact of the maternal condition to the offspring epigenome and later health consequences. Food Science and Human Wellness. 2013;2(1):1-11. DOI: 10.1016/j.fshw.2013.03.002. 4. Ginsberg HN, Stalenhoef AFH. The metabolic syndrome: targeting dyslipidaemia to reduce coronary risk. J Cardiovasc Risk. 2003; 10(2):121-8. DOI: 10.1177/174182670301000207 DOI: 10.1097/00043798-200304000-00007. 5. Brudac I, Cucuianu M. Pathogenic role of abnormal fatty acids and adipokines in the portal flow. Relevance for the metabolic syndrome, hepatic steatosis and steatohepatitis. Rom J Int Med. 2007;45:149-57. 6. Frazier-Wood AC, Aslibekyan S, Absher DM, Hopkins PH, Sha J, Tsai MY, et al. Methylation at CPT1A locus is associated with lipoprotein subfraction profiles. J Lipid Res. 2014;55(7):1324-30. DOI: 10.1194/jlr.M048504. 7. Mendelson M, Liang L, Chen J, Baccarelli A, Hirschhorn JN, S.K. Osganian SK, de Ferranti SD. Epigenetic modifications associated with dyslipidemia among obese children and adolescents. CJC. 2014;30(10):S190-1. 8. Mamtani M, Kulkarni H, Dyer T, Gring HH, Neary JL, Cole SA, et al. Genome- and epigenome-wide association study of hypertriglyceridemic waist in Mexican American families. Clin Epigenetics. 2016 Jan 20;8:6. DOI: 10.1186/s13148-016-0173-x. 9. Lopez-Legarrea P Continue reading >>

Lipid Metabolism In Gestational Diabetes

Lipid Metabolism In Gestational Diabetes

You have reached the maximum number of saved studies (100). Please remove one or more studies before adding more. The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. ClinicalTrials.gov Identifier: NCT00534105 Results First Posted : September 11, 2013 Information provided by (Responsible Party): Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information The purpose of this pilot study is to determine if, during pregnancy, women with GDM have an exaggerated lipid response compared to non-gestational diabetics. If a difference is noted, further studies will explore the possibility of screening gestational diabetics during their pregnancy for hyperlipidemia to determine if prenatal screening can predict postpartum risk for hyperlipidemia. In addition the relationship, if any between maternal lipid dysfunction and placental disease will be explored. This will be a prospective cohort study. As part of routine prenatal care, women receive a one hour glucose challenge test to screen for gestational diabetes. Those women with elevated values then require a three hour glucose tolerance test, which is a diagnostic test for gestational diabetes. All women that are scheduled to receive a three hour GTT will be identified and ask to enroll in this study. 46 women whose three hour GTT is normal and thus do not have GDM, will be compared to 46 women with an abnormal three hour GTT and thus would have the diagnosis of GDM. Enrolled women will have a lipid panel consisting of; total cholesterol, triglycerides, HDL and LDL cholesterol at the time Continue reading >>

High Risk Of Lipoprotein Dysfunction In Type 2 Diabetes Mellitus

High Risk Of Lipoprotein Dysfunction In Type 2 Diabetes Mellitus

Rev Esp Cardiol. 2008;8(Supl C):18-24 - Vol. 8 Num.Supl.C High Risk of Lipoprotein Dysfunction in Type 2 Diabetes Mellitus a Professor of Medicine and Endocrinology. University of Valencia. Valencia. Spain. Type 2 diabetes mellitus. Insulin resistance. Lipid metabolism. Diabetic dyslipidemia. Type 2 diabetes carries an elevated cardiovascular risk. A significant component of such risk can be attributed to diabetic dyslipidemia, a cluster of plasma lipid and lipoprotein abnormalities that are metabolically interrelated. Its main characteristics are elevated triglycerides, lowered high-density lipoproteins (HDL), and raised small, dense low-density lipoproteins (LDL) that are referred to as the "atherogenic lipid triad." Diabetic dyslipidemia is associated with insulin resistance, visceral obesity and liver fat content. Insulin resistance is related to excessive flux of substrates (ie, free fatty acids, FFA) for very low density lipoproteins (VLDL) assembly in the liver, as well as the upregulation of the machinery generating large VLDL1 particles in excess. The recognition that the elevation of large VLDL1 particles initiates a sequence of events leading to the formation of small dense LDL and HDL species has focused the assembly of VLDL particles on the spotlight as a potential culprit of diabetic dyslipidemia. Other components of the atherogenic lipid profile are elevated apoB, prolonged postprandial lipemia and accumulation of remnant particles in the circulation. Different prospective trials with statins have proven effective in the treatment of diabetic dyslipidemia but the residual cardiovascular risk remains high. Future trials with new lipid-lowering and antidiabetic agents will hopefully allow more targeted treatment of lipid disorders and postprandial lipemia Continue reading >>

Lipid Metabolism In The Etiology Of Type 2 Diabetes Esser, Victoria University Of Texas Sw Medical Center Dallas, Dallas, Tx, United States

Lipid Metabolism In The Etiology Of Type 2 Diabetes Esser, Victoria University Of Texas Sw Medical Center Dallas, Dallas, Tx, United States

Lipid Metabolism in the Etiology of Type 2 Diabetes (Scanned from the applicant's description) Type 2 diabetes mellitus has major clinical and social impact, but its underlying pathophysiology is poorly understood. Since the disease is diagnosed as a disorder of carbohydrate metabolism, i.e., hyperglycemia, the possible contribution of abnormal lipid metabolism to its etiology has been largely overlooked. The predominant, obesity-related form of diabetes is characterized by hyperinsulinemia, resistance to insulin-mediated glucose disposal in skeletal muscle, and elevated plasma free fatty acid and triglyceride levels. It has been suggested that a derangement of lipid metabolism is an early event contributing to the development of both hyperinsulinemia and insulin resistance. Our laboratory has demonstrated the essential role that plasma fatty acids play in sustaining normal glucose-stimulated insulin secretion in fasted subjects, and has also utilized novel 1-H NMR spectroscopic techniques to illustrate the strong correlation between intramyocellular lipid (IMCL) content and skeletal muscle insulin resistance. In the current proposal, we seek to expand on this theme by investigating the effects of high-fat feeding, pharmacologic inhibition of lipid oxidation, and leptin administration on insulin secretion and insulin sensitivity in rats and determining how these changes might be linked to alterations in muscle and islet triglyceride content. Because deficiencies of leptin and/or leptin signaling can precipitate the development of obesity/diabetes mellitus, it is conceivable that the primary function of leptin is to control lipid oxidation and lipolysis in a manner that prevents tissue lipid accumulation, thus maintaining normal glucose metabolism. We will administer le Continue reading >>

Insulin Resistance And Lipid Disorders

Insulin Resistance And Lipid Disorders

Roberto Miccoli; Cristina Bianchi; Giuseppe Penno; Stefano Del Prato Dysregulation of Lipid Metabolism and Insulin Resistance Whilst current definitions may still define insulin resistance in terms of insulin effects on glucose metabolism, the last decade has seen a shift from the traditional 'glucocentric' view of the syndrome associated with insulin resistance to an increasingly acknowledged 'lipocentric' viewpoint. The notion that lipids may act as signaling factors that regulate metabolic functions in target tissues was first suggested more than 40 years ago, when Randle et al. hypothesized that obesity-associated insulin resistance could be explained by substrate competition between increased circulating NEFA and glucose for oxidative metabolism in insulin-responsive cells. The importance of NEFA and lipid metabolism was also outlined by McGarry, who suggested that insulin resistance and concomitant hyperglycemia could be viewed in the context of underlying abnormalities of lipid metabolism.[ 67 ] More recently, glucose uptake, rather than intracellular glucose metabolism, has been implicated as a rate-limiting step for NEFA-induced insulin resistance.[ 68 ] In this model, NEFA and some of their metabolites, including acyl-CoA, ceramides and diacyglycerol, have been demonstrated to serve as signaling molecules that activate protein kinases such as PKC, JNK and IKK. These kinases can impair insulin signaling by increasing inhibitory serine phosphorylation of insulin receptor substrates (IRS), the key mediators of insulin signaling, and activating an inflammatory response.[ 68 ] In such a lipocentric framework, the term lipotoxicity was introduced by Unger to describe the deleterious effect of TG accumulation in pancreatic -cells, resulting in impaired glucose-stimu Continue reading >>

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