Home About us Contact
|
Home About us Contact | ||
|
|
||
Insulin Resistance (insulin + resistance)
Kinds of Insulin Resistance Terms modified by Insulin Resistance Selected AbstractsDO PLASMA NON-ESTERIFIED FATTY ACIDS AND INSULIN RESISTANCE CONTRIBUTE TO IMPAIRED ENDOTHELIAL FUNCTION IN NEPHROTIC SYNDROME?NEPHROLOGY, Issue 1 2002G. Dogra [source] IMPACT OF OBESITY AND INSULIN RESISTANCE ON VASOMOTOR TONE: NITRIC OXIDE AND BEYONDCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2006David W Stepp SUMMARY 1Obesity is rapidly increasing in Western populations, driving a parallel increase in hypertension, diabetes and vascular disease. Prior to the development of overt diabetes or hypertension, obese patients spend years in a state of progressive insulin resistance and metabolic disease. Mounting evidence suggests that this insulin-resistant state has deleterious effects on the control of blood flow, thus placing organ systems at a higher risk for end-organ damage and increasing cardiovascular mortality. 2The purpose of the present review is to examine the current literature on the effects of obesity and insulin resistance on the acute control of vascular tone. Effects on nitric oxide (NO)-mediated control of vascular tone are particularly examined with regard to proximal causes and distal mechanisms of the impaired NO-mediation of vasodilation. 3Finally, novel pathways of impaired control of perfusion are summarized from the recent literature to identify new avenues of exploring impaired vascular function in patients with metabolic disease. [source] Initial short-term intensive insulin therapy as a strategy for evaluating the preservation of beta-cell function with oral antidiabetic medications: a pilot study with sitagliptinDIABETES OBESITY & METABOLISM, Issue 10 2010R. Retnakaran Aim: Studies evaluating the effects of oral antidiabetic drugs (OADs) on beta-cell function in type 2 diabetes mellitus (T2DM) are confounded by an inability to establish the actual baseline degree of beta-cell dysfunction, independent of the deleterious effects of hyperglycaemia (glucotoxicity). Because intensive insulin therapy (IIT) can induce normoglycaemia, we reasoned that short-term IIT could enable evaluation of the beta-cell protective capacity of OADs, free from confounding hyperglycaemia. We applied this strategy to assess the effect of sitagliptin on beta-cell function. Methods: In this pilot study, 37 patients with T2DM of 6.0 + 6.4 years duration and A1c 7.0 + 0.8% on 0,2 OADs were switched to 4,8 weeks of IIT consisting of basal detemir and premeal insulin aspart. Subjects achieving fasting glucose <7.0 mmol/l 1 day after completing IIT (n = 21) were then randomized to metformin with either sitagliptin (n = 10) or placebo (n = 11). Subjects were followed for 48 weeks, with serial assessment of beta-cell function [ratio of AUCCpep to AUCgluc over Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) (AUCCpep/gluc/HOMA-IR)] on 4-h meal tests. Results: During the study, fasting glucagon-like-peptide-1 was higher (p = 0.003) and A1c lower in the sitagliptin arm (p = 0.016). Nevertheless, although beta-cell function improved during the IIT phase, it declined similarly in both arms over time (p = 0.61). By study end, AUCCpep/gluc/HOMA-IR was not significantly different between the placebo and sitagliptin arms (median 71.2 vs 80.4; p = 0.36). Conclusions: Pretreatment IIT can provide a useful strategy for evaluating the beta-cell protective capacity of diabetes interventions. In this pilot study, improved A1c with sitagliptin could not be attributed to a significant effect on preservation of beta-cell function. [source] Prevalence of the metabolic syndrome in the island of Gran Canaria: comparison of three major diagnostic proposalsDIABETIC MEDICINE, Issue 12 2005M. Boronat Abstract Aims The present study was conducted to estimate the prevalence of the metabolic syndrome in a Canarian population, and to compare its frequency as defined by the most commonly used working definitions. Methods Cross-sectional population-based study. One thousand and thirty adult subjects were randomly selected from the local census of Telde, a city located on the island of Gran Canaria. Participants completed a survey questionnaire and underwent physical examination, fasting blood analyses, and a 75-g standardized oral glucose tolerance test. The prevalence of the metabolic syndrome was estimated according to the definitions proposed by the World Health Organization (WHO), the European Group for the Study of Insulin Resistance (EGIR) and the National Cholesterol Education Program (NCEP), the latter with the original (6.1 mmol/l) and the revised criterion (5.6 mmol/l) for abnormal fasting glucose. Results The adjusted prevalence of the metabolic syndrome was 28.0, 15.9, 23.0 and 28.2%, using the WHO, EGIR, NCEP and revised NCEP criteria, respectively. The measure of agreement (, statistic) was 0.57 between the WHO and the original NCEP definitions, and 0.61 between the WHO and the revised NCEP definitions. After excluding diabetic subjects, the agreement between the EGIR and WHO proposals was fairly good (, = 0.70), whereas concordance of the EGIR with the original and the revised NCEP definitions was moderate (, = 0.47 and 0.46, respectively). Conclusions Whichever the considered diagnostic criteria, the prevalence of the metabolic syndrome in this area of the Canary Islands is greater than that observed in most other European populations. [source] Effect of recombinant human erythropoietin on insulin resistance in hemodialysis patientsHEMODIALYSIS INTERNATIONAL, Issue 3 2009Essam KHEDR Abstract Insulin resistance is a characteristic feature of uremia. Insulin resistance and concomitant hyperinsulinemia are present irrespective of the type of renal disease. Treatment with recombinant human erythropoietin (rHuEPO) was said to be associated with improvement in insulin sensitivity in uremic patients. The aim of this study was to compare insulin resistance in adult uremic hemodialysis (HD) patients including diabetic patients treated with or without rHuEPO. A total of 59 HD patients were studied, patients were divided into 2 groups of subjects: 30 HD patients on regular rHuEPO treatment (group A), and 29 HD patients not receiving rHuEPO (group B) diabetic patients were not excluded. Full medical history and clinical examination, hematological parameters, lipid profile, serum albumin, parathyroid horomone, Kt/V, fasting glucose, and insulin levels were measured in all subjects. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was used to compare insulin resistance. The results of this study showed that the mean insulin level of HD patients treated with rHuEPO (group A) (17.5 ± 10.6 ,U/mL) was significantly lower than patients without rHuEPO (group B) (28.8 ± 7.7 ,U/mL), (P<0.001). Homeostasis Model Assessment of Insulin Resistance levels in group A were significantly lower than in group B (3.8 ± 2.97, 7.98 ± 4.9, respectively, P<0.001). Insulin resistance reflected by HOMA-IR levels among diabetic patients in group A was significantly lower than among diabetic patients in group B (3.9 ± 3.2, 9.4 ± 7.2, respectively, P<0.001). Also, HOMA-IR levels among nondiabetic patients in group A were significantly lower than among nondiabetic patients in group B (3.7 ± 2.85, 6.9 ± 1.43, respectively, P<0.01). We found a statistically significant negative correlation between duration of erythropoietin treatment, fasting blood glucose, insulin levels, and insulin resistance (r=,0.62, ,0.71, and ,0.57, P<0.001). Patients treated with rHuEPO showed less insulin resistance compared with patients not treated with rHuEPO in diabetic and nondiabetic patients and, duration of erythropoietin treatment is negatively correlated with insulin levels and insulin resistance in HD patients. [source] Diverse Effect of Inflammatory Markers on Insulin Resistance and Insulin-Resistance Syndrome in the ElderlyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 3 2004Angela M. Abbatecola MD Objectives: To evaluate the potential association between different inflammatory markers and insulin resistance (IR), as well as insulin-resistance syndrome (IRS) in a large, population-based study of older, nondiabetic persons. Design: Cross-sectional study. Setting: Outpatient clinic in Greve in Chianti and Bagno a Ripoli (Italy). Participants: One thousand one hundred forty-six nondiabetic subjects ranging in age from 22 to 104. Measurements: Anthropometric measurements; plasma fasting levels of glucose, insulin, and cholesterol (total, high-density lipoprotein, low-density lipoprotein); homeostasis model assessment to estimate degree of insulin resistance; tumor necrosis factor , (TNF-,), interleukin 6 (IL-6), soluble IL-6 receptor (sIL-6R), interleukin receptor antagonist (IL-1ra), and C-reactive protein (CRP) plasma concentrations; diastolic, systolic, and mean arterial blood pressure; and echo-color-Doppler duplex scanning examination of carotid arteries. Results: Insulin resistance correlated with age (r=0.102; P<.001) and plasma levels of TNF-, (r=0.082; P=.007), IL-1ra (r=0.147; P<.001), IL-6 (r=0.133; P<.001), sIL-6R (r=,0.156; P<.001), and CRP (r=0.83; P<.001). Subjects in the upper tertile of IR degree were older and had higher serum levels of TNF-,, IL-1ra, and IL-6 and lower levels of sIL-6R than subjects in the lowest tertile. Independent of age, sex, body mass index, waist-to-hip ratio, triglycerides, drug intake, diastolic blood pressure, smoking habit, and carotid atherosclerotic plaques, higher IL-6 (t=2.987; P=.003) serum concentrations were associated with higher IR, whereas sIL-6R levels (t=,5.651; P<.001) were associated with lower IR. Furthermore, IL-1ra concentrations (t=2.448; P=.015) were associated with IRS, and higher sIL-6R plasma levels continued to correlate negatively with IRS. Conclusion: Different inflammatory markers are associated with a diverse effect on IR and IRS in elderly nondiabetic subjects. [source] Original Paper: Telmisartan Effects on Insulin Resistance in Obese or Overweight Adults Without Diabetes or HypertensionJOURNAL OF CLINICAL HYPERTENSION, Issue 9 2010Willa Hsueh MD J Clin Hypertens (Greenwich). 2010;12:746,752. ©2010 Wiley Periodicals, Inc. Angiotensin receptor blockers (ARBs) are antihypertensive agents associated with reduced risk of new-onset diabetes mellitus. The ARB telmisartan is a partial agonist of peroxisome proliferator,activated receptor-gamma (PPAR-,). This study evaluated the effect of telmisartan on insulin resistance, a known target of PPAR-, agonism. Overweight/obese persons with body mass index ,28 kg/m2, waist circumference ,35 inches, and components of the metabolic syndrome without hypertension or diabetes who were not preselected for insulin resistance were enrolled. Patients were randomized to telmisartan or matching placebo for 16 weeks. The primary efficacy measure was changed from baseline in the insulin sensitivity index (SI), calculated from oral glucose tolerance testing. SI was also evaluated in a subset of patients using a hyperinsulinemic euglycemic clamp. Secondary end points included measures of insulin sensitivity and glucose and lipid metabolism. A total of 138 patients were randomized and received ,1 dose of study medication; 128 completed the study. At end point, no significant difference was found between telmisartan and placebo groups regarding change from baseline in SI or in glucose area under the curve. No significant between-group differences were found regarding glucose metabolism or lipoprotein levels. In the population with abdominal obesity and components of the metabolic syndrome, telmisartan did not increase insulin sensitivity. [source] Adiponectin Is a Link Among Inflammation, Insulin Resistance, and High-Density Lipoprotein Cholesterol But Is Not Associated With Paraoxonase Activity in Premenopausal WomenJOURNAL OF CLINICAL HYPERTENSION, Issue 11 2009Pinar Cetinalp-Demircan PhD The aim of this study was to evaluate whether insulin sensitivity, inflammatory response, and plasma lipid profile are associated with circulating adiponectin levels in nondiabetic healthy women. The authors also assessed whether adiponectin has any effect on high-density lipoprotein cholesterol,linked paraoxonase 1 (PON-1) activity and on the susceptibility of low-density lipoproteins to oxidation. Plasma adiponectin was measured in 91 nondiabetic premenopausal women, and the patients were then divided into quartiles. Circulating adiponectin was found to be associated with body mass index (r=.55, P<.001). After adjustment for body mass index, adiponectin showed an inverse correlation with the homeostasis model assessment of insulin resistance (HOMA-IR) (r=,.41, P<.001) and a positive correlation with high-density lipoprotein cholesterol (r=.43, P<.001). In linear regression analysis, HOMA-IR, tumor necrosis factor ,, and high-density lipoprotein cholesterol levels were found to be independently associated with adiponectin. However, high-density lipoprotein cholesterol,linked PON-1 activity and the susceptibility of low-density lipoproteins to in vitro oxidation did not seem to be related to plasma adiponectin concentrations. [source] Hydroxypropylated Tapioca Starch Retards the Development of Insulin Resistance in KKAy Mice, a Type 2 Diabetes Model, Fed a High-Fat DietJOURNAL OF FOOD SCIENCE, Issue 7 2009Makoto Tachibe ABSTRACT:, The hypoglycemic and antidiabetic effect of hydroxypropyl tapioca starch (HPTS, degree of substitution = 0.180) was investigated in male KKAy mice. Mice were fed a purified high-fat (20%) diet without or with HPTS (5% or 10%) for 33 d. Gelatinized tapioca starch (TS) was used as a reference. Fasting blood glucose concentrations, days 14 and 28, were significantly lower in the 10% HPTS group compared with the reference. In an oral glucose tolerance test (OGTT), day 28, blood glucose concentrations in the 5% HPTS group, at 60, 90, and 120 min, and in the 10% HPTS group, at 30, 60, and 90 min after oral administration of glucose, were significantly lower compared with the reference. The area under the glucose curve (AUC) for glucose in both HPTS groups was significantly lower compared with the reference. Energy intake was significantly lower in the 10% HPTS group compared with the reference. At the end of the experiment, adiponectin concentrations were significantly higher in the 10% HPTS group compared with the reference. A homeostasis model assessment of insulin resistance (HOMA-IR) tended to be lower in the 10% HPTS group compared with the reference, whereas a quantitative insulin sensitivity check index (QUICKI) was significantly higher in both HPTS groups compared with the reference. These results show that HPTS retards the development of insulin resistance in KKAy mice fed a high-fat diet. [source] High-Hydroxypropylated Tapioca Starch Improves Insulin Resistance in Genetically Diabetic KKAy MiceJOURNAL OF FOOD SCIENCE, Issue 3 2009R. Kato ABSTRACT:, The hypoglycemic and antidiabetic effect of hydroxypropyl tapioca starch (HPTS) with a varying degree of substitution (DS: 0.058, 0.091, and 0.180) was investigated in rats and KKAy mice, an animal model of type 2 diabetes. The positive incremental area under the curve (IAUC) for glucose significantly decreased as the DS of HPTS increased. The IAUC after intragastric intubation of the highest HPTS (HPTS-III, DS = 0.180) was 55% of the IAUC of tapioca starch (TS). After 28 d, fasting blood glucose and insulin concentrations were significantly lower in rats fed HPTS-III (50 g/kg diet) than in those fed TS (P < 0.05). In KKAy mice fed HPTS-III (50 or 100 g/kg diet) for 33 d, as compared with TS, there was a delay in the detection of glucose in urine and also a decreased incidence of finding glucose in urine on days 7, 21, and 28; in addition, the AUCs for glucose in the oral glucose tolerance test on days 14 and 28 were significantly lower (P < 0.05 and P < 0.05, respectively). The plasma adiponectin concentration and the quantitative insulin sensitivity check index (QUICKI) were significantly higher in mice fed HPTS-III than in those fed TS (P < 0.01), whereas the homeostasis model assessment of insulin resistance (HOMA-IR) was lower (P < 0.01). Energy intake was significantly lower in mice fed HPTS-III than in those fed TS. These findings show that HPTS with a high DS resists digestion by ,-amylase and improves insulin resistance in KKAy mice by decreasing energy intake. However, the potential mechanism by which HPTS-III decreases energy intake is unclear at present. [source] The Role of the Flushing Response in the Relationship Between Alcohol Consumption and Insulin ResistanceALCOHOLISM, Issue 10 2010Jin-Gyu Jung Background:, Facial flushing responses to drinking, because of intolerance to alcohol, are observed in some people, especially Asians. This study examined the role of flushing responses in the relationship between alcohol consumption and insulin resistance (IR). Methods:, Participants in this cross-sectional analysis included 624 Korean men (80 nondrinkers, 306 nonflushing drinkers, and 238 flushing drinkers) who were free of cardiovascular disease and diabetes. Data on the flushing response to drinking and alcohol consumption were collected from medical records. IR was estimated using the Homeostasis Model Assessment (HOMAIR). On the basis of comparisons with nondrinkers, the risk of IR according to the quantity of alcohol consumed per week was analyzed among nonflushers and flushers. Results:, After adjusting for age, exercise status, smoking status, BMI, waist circumference, blood pressure, high-density lipoprotein cholesterol, and triglycerides using a logistic regression model, we found a low risk of IR among nonflushers who consumed ,4 drinks (1 drink = 14 g of alcohol) per week (OR = 0.3). In contrast, a higher risk of IR was associated with nonflushers who consumed >20 drinks per week (OR = 3.5). On the other hand, only a higher risk of IR was associated with flushers who consumed >12 drinks per week (>12 to 20 drinks: OR = 4.7; >20 drinks: OR = 3.5). Conclusions:, The amount of drinking associated with the development of IR in flushers was lower than in nonflushers. Additionally, no positive effect of moderate drinking on IR was observed in flushers. The findings support acetaldehyde-derived mechanisms in the development of alcohol-related IR. [source] Chronic Ethanol-Induced Insulin Resistance Is Associated With Macrophage Infiltration Into Adipose Tissue and Altered Expression of AdipocytokinesALCOHOLISM, Issue 9 2007Li Kang Background:, Chronic ethanol consumption disrupts glucose homeostasis and is associated with the development of insulin resistance. While adipose tissue and skeletal muscle are the two major organs utilizing glucose in response to insulin, the relative contribution of these two tissues to impaired glucose homeostasis during chronic ethanol feeding is not known. As other models of insulin resistance, such as obesity, are characterized by an infiltration of macrophages into adipose tissue, as well as changes in the expression of adipocytokines that play a central role in the regulation of insulin sensitivity, we hypothesized that chronic ethanol-induced insulin resistance would be associated with increased macrophage infiltration into adipose tissue and changes in the expression of adipocytokines by adipose tissue. Methods:, Male Wistar rats were fed a liquid diet containing ethanol as 36% of calories or pair-fed a control diet for 4 weeks. The effects of chronic ethanol feeding on insulin-stimulated glucose utilization were studied using the hyperinsulinemic-euglycemic clamp technique, coupled with the use of isotopic tracers. Further, macrophage infiltration into adipose tissue and expression of adipocytokines were also assessed after chronic ethanol feeding. Results:, Hyperinsulinemic-euglycemic clamp studies revealed that chronic ethanol feeding to rats decreased whole-body glucose utilization and decreased insulin-mediated suppression of hepatic glucose production. Chronic ethanol feeding decreased glucose uptake in epididymal, subcutaneous, and omental adipose tissue during the hyperinsulinemic-euglycemic clamp, but had no effect on glucose disposal in skeletal muscle. Chronic ethanol feeding increased the infiltration of macrophages into epididymal adipose tissue and changed the expression of mRNA for adipocytokines: expression of mRNA for monocyte chemoattractant protein 1, tumor necrosis factor ,, and interleukin-6 were increased, while expression of mRNA for retinol binding protein 4 and adiponectin were decreased in epididymal adipose tissue. Conclusions:, These data demonstrate that chronic ethanol feeding results in the development of insulin resistance, associated with impaired insulin-mediated suppression of hepatic glucose production and decreased insulin-stimulated glucose uptake into adipose tissue. Chronic ethanol-induced insulin resistance was associated with increased macrophage infiltration into adipose tissue, as well as changes in the expression of adipocytokines by adipose tissue. [source] Alcohol-Induced Disruption of Endocrine SignalingALCOHOLISM, Issue 8 2007Martin J. J. Ronis This article contains the proceedings of a symposium at the 2006 ISBRA Meeting in Sydney Australia, organized and cochaired by Martin J. Ronis and Thomas M. Badger. The presentations were (1) Effect of Long-Term Ethanol Consumption on Liver Injury and Repair, by Jack R. Wands; (2) Alcohol-Induced Insulin Resistance in Liver: Potential Roles in Regulation of ADH Expression, Ethanol Clearance, and Alcoholic Liver Disease, by Thomas M. Badger; (3) Chronic Gestational Exposure to Ethanol Causes Brain Insulin and Insulin-Like Growth Factor Resistance, by Suzanne M de la Monte; (4) Disruption of IGF-1 Signaling in Muscle: A Mechanism Underlying Alcoholic Myopathy, by Charles H. Lang; (5) The Role of Reduced Plasma Estradiol and Impaired Estrogen Signaling in Alcohol-Induced Bone Loss, by Martin J. Ronis; and (6) Short-Term Influence of Alcohol on Appetite-Regulating Hormones in Man, by Jan Calissendorff. [source] Obesity, Insulin Resistance, and Microvessel DensityMICROCIRCULATION, Issue 4-5 2007Jefferson C. Frisbee ABSTRACT The growing incidence and prevalence of the overweight/obese condition across developed economies worldwide has an enormous impact on increasing the risk for the development of impaired glycemic control or insulin resistance and ultimately peripheral vascular disease (PVD) in afflicted individuals. This places an enormous economic and social burden on these societies, in terms of additional health care costs and lost productivity and through a reduction in the quality of life of the individual owing, in part, to the progressive PVD. Characterized by an inability of the vascular systems to adequately perfuse tissues and organs relative to their metabolic demand, PVD is in part a function of a structural remodeling of the microvascular networks such that the density of microvessel and capillaries within tissues is reduced below that under normal conditions, with the potential for profound negative impacts on the processes of mass transport and exchange. The review discusses the severity of the obesity "epidemic" from the perspective of PVD and the effects of the development of the obese, insulin-resistant condition on tissue/organ microvessel density. Additional material is reviewed that addresses ameliorative treatments, primarily exercise training, on blunting microvessel loss in the obese, insulin-resistant individual, and on potential mechanistic contributors that warrant considerable future investigation. [source] Obesity, Insulin Resistance, and Capillary RecruitmentMICROCIRCULATION, Issue 4-5 2007Stephen Rattigan ABSTRACT Objective: Insulin has vascular actions within the skeletal muscle microcirculation (capillary recruitment) that enhance its own access and that of glucose to the muscle cells. Obesity and insulin resistance are associated with dysregulated vascular function within muscle and a loss of insulin-mediated capillary recruitment. Furthermore, agents that impair insulin's vascular actions to recruit capillaries lead to acute insulin resistance in terms of muscle glucose uptake. Together these data suggest a strong connection between the loss of insulin-mediated capillary recruitment and the development of insulin resistance. This review examines the mechanisms involved in insulin-mediated capillary recruitment and the vascular defects associated with obesity and insulin resistance that may impair the capillary recruiting process. Understanding the mechanisms of insulin-mediated capillary recruitment and its impairment may lead to new treatment avenues to prevent the progression of obesity to diabetes. [source] Influence of Glucose Control and Improvement of Insulin Resistance on Microvascular Blood Flow and Endothelial Function in Patients with Diabetes Mellitus Type 2MICROCIRCULATION, Issue 7 2005THOMAS FORST ABSTRACT Objective: The study was performed to investigate the effect of improving metabolic control with pioglitazone in comparison to glimepiride on microvascular function in patients with diabetes mellitus type 2. Methods: A total of 179 patients were recruited and randomly assigned to one treatment group. Metabolic control (HbA1c), insulin resistance (HOMA index), and microvascular function (laser Doppler fluxmetry) were observed at baseline and after 3 and 6 months. Results: HbA1c improved in both treatment arms (pioglitazone: 7.52 ± 0.85% to 6.71 ± 0.89%, p < .0001; glimepiride: 7.44 ± 0.89% to 6.83 ± 0.85%, p < .0001). Insulin-resistance decreased significantly in the pioglitazone group (6.15 ± 4.05 to 3.85 ± 1.92, p < .0001) and remained unchanged in the glimepiride group. The microvascular response to heat significantly improved in both treatment groups (pioglitazone 48.5 [15.2; 91.8] to 88.8 [57.6; 124.1] arbitrary units [AU], p < .0001; glimepiride 53.7 [14.1; 91.9] to 87.9 [52.9, 131.0] AU, p < .0001, median [lower and upper quartile]). Endothelial function as measured with the acetylcholine response improved in the pioglitazone group (38.5 [22.2; 68.0] to 60.2 [36.9; 82.8], p = .0427) and remained unchanged in the glimepiride group. Conclusions: Improving metabolic control has beneficial effects in microvascular function in type 2 diabetic patients. Treatment of type 2 diabetic patients with pioglitazone exerts additional effects on endothelial function beyond metabolic control. [source] Trans Fatty Acids, Insulin Resistance, and Type 2 DiabetesNUTRITION REVIEWS, Issue 8 2006Andrew O. Odegaard BA Type 2 diabetes, a growing global health problem, has a complex etiology involving many interactions between genetic and environmental factors. Essential to the development of the disease is insulin resistance of the peripheral tissues. Insulin resistance may be partly modified by the specific types of dietary fatty acids. Trans fatty acids (TFAs), created through the transformation of polyunsaturated fatty acids from their natural cis form to the trans form, are abundant in the Western diet. TFAs take on similar properties as saturated fats, and appear to be more atherogenic. High intakes of saturated fats may promote insulin resistance. It is therefore reasonable to hypothesize that high intakes of TFAs would have similar, or stronger, effects. In this review, all current evidence on the topic of TFAs, insulin resistance, and type 2 diabetes is summarized and interpreted. Although there is some support from observational and experimental studies for the hypothesis that high intakes of TFAs may increase the risk for type 2 diabetes, inconsistencies across studies and methodological problems make it premature to draw definitive conclusions at this time. More experimental research in humans is needed to further address this question. [source] Extreme Subcutaneous, Intramuscular and Inhaled Insulin Resistance Treated by Pancreas Transplantation AloneAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010J. R. Sa Diabetes mellitus with resistance to insulin administered subcutaneously or intramuscularly (DRIASM) is a rare syndrome and is usually treated with continuous intravenous insulin infusion. We present here two cases of DRIASM in 16 and 18 years female patients that were submitted to pancreas transplantation alone (PTA). Both were diagnosed with type 1 diabetes as young children and had labile glycemic control with recurrent episodes of diabetic ketoacidosis. They had prolonged periods of hospitalization and complications related to their central venous access. Exocrine and endocrine drainages were in the bladder and systemic, respectively. Both presented immediate graft function. In patient 1, enteric conversion was necessary due to reflux pancreatitis. Patient 2 developed mild postoperative hyperglycemia in spite of having normal pancreas allograft biopsy and that was attributed to her immunosuppressive regimen. Patient 1 died 9 months after PTA from septic shock related to pneumonia. In 8 months of follow-up, Patient 2 presented optimal glycemic control without the use of antidiabetic agents. In conclusion, PTA may be an alternative treatment for DRIASM patients. [source] Insulin Resistance, Serum Adipokines and Risk of Fibrosis Progression in Patients Transplanted for Hepatitis CAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2009B. J. Veldt In the nontransplant setting diabetes mellitus is a risk factor for disease progression in patients with chronic hepatitis C virus (HCV) infection. The impact of early insulin resistance on the development of advanced fibrosis, even in the absence of clinically apparent diabetes mellitus, is not known. Our aim was to determine whether the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) can be used to identify insulin-resistant patients at risk for rapid fibrosis progression. Cohort study including patients transplanted for chronic HCV between January 1, 1995 and January 1, 2005. One hundred sixty patients were included; 25 patients (16%) were treated for diabetes mellitus and 36 patients (23%) were prediabetic, defined as HOMA-IR >2.5. Multivariate Cox regression analysis showed that insulin resistance (hazard ratio (HR) 2.07; confidence interval (CI) 1.10,3.91, p = 0.024), donor age (HR 1.33;CI 1.08,1.63, p = 0.007) and aspartate aminotransferase (HR 1.03;CI 1.01,1.05, p < 0.001) were significantly associated with a higher probability of developing advanced fibrosis, i.e. Knodell fibrosis stage 3 or 4, whereas steatosis (HR 0.94;CI 0.46,1.92, p = 0.87) and acute cellular rejection (HR 1.72;CI 0.88,3.36, p = 0.111) were not. In conclusion, posttransplant insulin resistance is strongly associated with more severe recurrence of HCV infection. HOMA-IR is an important tool for the identification of insulin resistance among patients at risk for rapid fibrosis progression after liver transplantation for HCV. [source] Apolipoprotein C-III and E Polymorphisms and Cardiovascular Syndrome, Hyperlipidemia, and Insulin Resistance in Renal TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2002Emilio Rodrigo Hyperlipidemia and insulin resistance frequently develop after renal transplantation, contributing to cardiovascular disease. Individual differences in response based upon genetic variations in proteins regulating lipidic and glucose tolerance metabolism could be expected. In the general population, the S2 allelic variant of the apoprotein (apo) C-III gene has been associated with hypertriglyceridemia and an insulin resistant state, whereas the E4 allele of the apo E has been associated with hypercholesterolemia and atherosclerosis. Its influence in renal transplant patients remains to be seen. In order to assess the impact of apo E and C-III major polymorphisms on atherosclerotic vascular disease, lipid profile and impaired glucose tolerance in renal transplant patients, we studied 110 consecutively examined patients undergoing kidney transplantation (age range 24,73 years). Atherosclerotic complications were detected in 25% of patients, with age, male sex and hypercholesterolemia being significant atherosclerotic risk factors. Among the male patients with E4 allele, the odds ratio for coronary disease and global atherosclerosis were 10.2 (95% CI) and 6.4 (95% CI), respectively. There were no significant differences in the frequency of any of the polymorphisms among patients with dyslipidemia and impaired glucose tolerance. As the number of patients in our sample was small, larger studies are needed to verify these issues. While in the studied population C-III polymorphism appears to have little association with the prevalence of atherosclerotic complications, E4 allele should be considered as a genetic marker of coronary artery disease and global atherosclerosis in renal transplant patients. [source] Insulin resistance among Brazilian schoolchildren: association with risk factors for cardiovascular diseasesACTA PAEDIATRICA, Issue 10 2009MWL Strufaldi Abstract Aim:, Our purpose was to evaluate Insulin Resistance (IR) and its association with risk factors for cardiovascular diseases (CVDs) among 161 (6- to 10-year-old) schoolchildren. Methods:, This two-stage cross-sectional study evaluated: BMI, blood pressure, personal history (birth weight) and family history of CVDs. Children with at least one of the following criteria participated in the second stage: obesity, personal or family history. Insulin resistance was determined using Homeostasis Model Assessment (HOMA). Results:, The HOMA distribution in terciles showed mean values for the first, second and third tercile of 0.41, 0.79 and 2.11 respectively. The HOMA distribution in the third tercile demonstrated statistically significant associations with overweight/obesity (p = 0.007), hypertension (p = 0.008) and low HDL (p = 0.02). Analysis of mean birth weight in each tercile and between terciles did not present any positive correlation (p = 0.213). Conclusion:, Higher levels of HOMA (IR) were positively associated with risk factors for CVD among schoolchildren. [source] Insulin resistance and fuel homeostasis: the role of AMP-activated protein kinaseACTA PHYSIOLOGICA, Issue 1 2009B. D. Hegarty Abstract The worldwide prevalence of type 2 diabetes (T2D) and related disorders of the metabolic syndrome (MS) has reached epidemic proportions. Insulin resistance (IR) is a major perturbation that characterizes these disorders. Extra-adipose accumulation of lipid, particularly within the liver and skeletal muscle, is closely linked with the development of IR. The AMP-activated protein kinase (AMPK) pathway plays an important role in the regulation of both lipid and glucose metabolism. Through its effects to increase fatty acid oxidation and inhibit lipogenesis, AMPK activity in the liver and skeletal muscle could be expected to ameliorate lipid accumulation and associated IR in these tissues. In addition, AMPK promotes glucose uptake into skeletal muscle and suppresses glucose output from the liver via insulin-independent mechanisms. These characteristics make AMPK a highly attractive target for the development of strategies to curb the prevalence and costs of T2D. Recent insights into the regulation of AMPK and mechanisms by which it modulates fuel metabolism in liver and skeletal muscle are discussed here. In addition, we consider the arguments for and against the hypothesis that dysfunctional AMPK contributes to IR. Finally we review studies which assess AMPK as an appropriate target for the prevention and treatment of T2D and MS. [source] Acupuncture: is it effective for treatment of insulin resistance?DIABETES OBESITY & METABOLISM, Issue 7 2010F. Liang Insulin resistance (IR) is closely associated with obesity, type 2 diabetes mellitus (T2DM), hypertension, polycystic ovary syndrome (PCOS), non-alcohol fatty liver diseases (NAFLD) and metabolic syndrome and is also a risk factor for serious diseases such as cardiovascular diseases. Pharmacological treatments available for IR are limited by drug adverse effects. Because acupuncture has been practiced for thousands of years in China, it has been increasingly used worldwide for IR-related diseases. This review analyses 234 English publications listed on the PubMed database between 1979 and 2009 on the effectiveness of acupuncture as a treatment for IR. These publications provide clinical evidence, although limited, in support of the effectiveness of acupuncture in IR. At this stage, well-designed, evidence-based clinical randomized controlled trial studies are therefore needed to confirm the effects of acupuncture on IR. Numerous experimental studies have demonstrated that acupuncture can correct various metabolic disorders such as hyperglycemia, overweight, hyperphagia, hyperlipidemia, inflammation, altered activity of the sympathetic nervous system and insulin signal defect, all of which contribute to the development of IR. In addition, acupuncture has the potential to improve insulin sensitivity. The evidence has revealed the mechanisms responsible for the beneficial effects of acupuncture, though further investigations are warranted. [source] Treatment of diabetic hypertensionDIABETES OBESITY & METABOLISM, Issue 5 2009David S. H. Bell Insulin resistance and hyperglycaemia combine to make hypertension more prevalent in the type 2 diabetic patient. Blood pressure goals below those for the non-diabetic subject have been shown to be more effective in lowering mortality and cardiovascular events in the diabetic patient. To achieve these goals in most cases, three to five antihypertensives from different therapeutic groups need to be utilized. Suppression of the renin,angiotensin system (RAS) with angiotensin-converting enzyme inhibitors, angiotensin 2 receptor blockers or a renin inhibitor should be the primary therapy. A second goal should be suppression of the sympathetic nervous system utilizing a beta-blocker that does not increase insulin resistance. The addition of a diuretic, calcium channel blocker or a vasodilator to suppressors of the RAS and sympathetic nervous system aid in achieving hypertensive goals in the diabetic patient. Achieving hypertensive goals with suppression of the RAS and sympathetic nervous system should result in a decrease in mortality and cardiovascular events in the diabetic hypertensive patient. In this review article, the benefits and disadvantages of the different antihypertensive therapies in the diabetic patient are discussed. [source] Effects of insulin resistance on endothelial function: possible mechanisms and clinical implicationsDIABETES OBESITY & METABOLISM, Issue 10 2008D Tousoulis Insulin resistance (IR) is defined as a reduced responsiveness of peripheral tissues to the effects of the hormone, referring to abated ability of insulin in stimulating glucose uptake in peripheral tissues and in inhibiting hepatic glucose output. Insulin has both a vasodilatory effect, which is largely endothelium dependent through the release of nitric oxide, and a vasoconstrictory effect through the stimulation of the sympathetic nervous system and the release of endothelin-1. IR and endothelial dysfunction (ED) are not only linked by common pathogenetic mechanisms, involving deranged insulin signalling pathways, but also by other, indirect to the hormone's actions, mechanisms. Different treatment modalities have been proposed to affect positively both the metabolic effects of insulin and ED. Weight loss has been shown to improve sensitivity to insulin as a result of either altered diet or exercise. Exercise has favourable effects on endothelial function in normal states and in states of disease, in men and women, and throughout the age spectrum and, hence, in IR states. Metformin improves sensitivity to insulin and most likely affects positively ED. Studies have shown that inhibitors of the renin,angiotensin system alter IR favourably, while Angiotensin converting enzyme (ACE) inhibitors and Angiotensin receptor type II (ATII) inhibitors improve ED. Ongoing studies are expected to shed more light on the issue of whether treatment with the thiazolidinediones results in improvement of endothelial function, along with the accepted function of improving insulin sensitivity. Finally, improved endothelial function by such treatments is not in itself proof of reduced risk for atherosclerosis; this remains to be directly tested in clinical trials. [source] Discordance between intramuscular triglyceride and insulin sensitivity in skeletal muscle of Zucker diabetic rats after treatment with fenofibrate and rosiglitazoneDIABETES OBESITY & METABOLISM, Issue 5 2007K. J. Nadeau Aim:, Intramyocellular triglyceride (IMTG) correlates with insulin resistance, but there is no clear causal relationship. Insulin resistance and associated hyperinsulinaemia may increase IMTG, via the insulin-regulated transcription factor, sterol regulatory element,binding protein 1 (SREBP-1). PPAR agonists may also affect IMTG via changes in insulin sensitivity, SREBP-1 or other factors. Methods:, We examined skeletal muscle IMTG and SREBP-1 expression, and metabolic parameters in Zucker diabetic fatty rats (ZDF) after 25 weeks of PPAR-, or PPAR-, administration. Results:, Compared with Zucker lean rats (ZL), untreated ZDF had significantly higher weights, serum glucose, insulin, free fatty acids, total cholesterol and triglycerides. IMTG and SREBP-1c messenger RNA (mRNA) were also higher in untreated ZDF; both were decreased by fenofibrate (FF). Rosiglitazone (Rosi), despite marked improvement in glycaemia, hyperinsulinaemia and hyperlipidaemia, failed to affect SREBP-1 expression, and increased body weight and IMTG. Rosi/FF combination caused less weight gain and no IMTG increase, despite metabolic effects similar to Rosi alone. Conclusions:, IMTG and SREBP-1c mRNA are high in the ZDF. FF and Rosi both improved insulin sensitivity but had opposite effects on IMTG. Thus, there was a clear discordance between insulin sensitivity and IMTG with PPAR agonists, indicating that IMTG and insulin sensitivity do not share a simple relationship. [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] 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] Insulin resistance and coronary artery disease: body mass index may have affected resultsDIABETES OBESITY & METABOLISM, Issue 1 2004Akheel A. Syed No abstract is available for this article. [source] Clustering of cardiovascular risk factors with diabetes in Chinese patients: the effects of sex and hyperinsulinaemiaDIABETES OBESITY & METABOLISM, Issue 3 2001Z. -R. SUMMARY Objective This study was designed to investigate factors which affect the clustering of cardiovascular risk factors with diabetes in Chinese patients. Research Design and Methods: Six hundred and fifty-four patients with diabetes were assessed comprehensively for diabetes complications and cardiovascular risk factors in a metropolitan hospital in Beijing, China. Insulin resistance and secretion were also evaluated by measurement of glucose and insulin levels before and after a meal tolerance test. Results were analysed according to patient groups stratified by the number of cardiovascular risk factors coexisting with diabetes. Results Cardiovascular risk factors were common in Chinese diabetic patients. The clustering of three or more of these factors with diabetes occurred more often than by chance alone and was associated with postprandial hyperinsulinaemia. Patients with a high number of risk factors were more prone to macrovascular events but did not have higher albuminuria. Using the commonly adopted lower threshold for diagnosing obesity and central obesity in women, there were more women with multiple risk factors. However, this disappeared if the same criteria were used for men and women. Even in the presence of diabetes, cardiovascular risk factors were inadequately controlled in most patients. Conclusions The concurrence of diabetes and other cardiovascular risk factors which constitute the metabolic syndrome is a common phenomenon in urban Chinese diabetic patients. It is associated with hyperinsulinaemia and possibly the female sex. This study emphasises the importance of public health measures to control cardiovascular risk factors in patients with diabetes. [source] | ||||||||||||||||||||||||||||||||||||||||