Index

Absorption inhibitors, for managing obesity, 176177 Acarbose, for managing carbohydrate levels in diabetes type 2, 199200 Acylation-stimulating protein (ASP), stimulation of triglyceride synthesis by, 4748 Adipocytes decrease in size of, in weight loss, 172 effects of, in endothelial dysfunction, 64 response to insulin, 26 visceral, metabolic activity of, 9293 Adipokinases, production of by adipose tissue, 911 adipose tissue, 40 Adiponectin clinical importance of, 4447 correlation with cardiovascular disease risk factors, 128 hepatoprotective effect of, 144 role in pathogenesis of metabolic syndrome, 92 Adipose tissue adipokinases produced by, 911, 40 defective esterification of fatty acids in, 103104 local glucocorticoid level in, 49 as an organ system, 26 products from, in obesity, 9394 proinflammatory mediators produced by, 3637 Adiposity, relationship with metabolic syndrome, 136141 Adipsin, increase of, in obesity, 50 -Adrenoceptor blockers. See Beta blockers Adult Treatment Panel-III (ATP III), 1, 21 algorithm for treating hypertension, 214 criteria for assessing risk for coronary heart disease, 155156 criteria for diagnosing metabolic syndrome, 115118, 127 in children and adolescents, 224 predictive power of, 131, 134 Age association with insulin resistance, 74 as a predictor of insulin resistance, 129 and prevalence of metabolic syndrome, 4

236

INDEX

Alcohol, role in prevention of coronary heart disease, 167168 American Association of Clinical Endocrinologists, criteria for diagnosing metabolic syndrome, 120122 American Diabetes Association (ADA), 24 revision of standards for impaired fasting glucose and impaired glucose tolerance, 68 American Heart Association (AHA) on causes of metabolic syndrome, 120 criterion for identifying overweight and obese children, 230 Nutrition Committee recommendation on soy protein in the diet, 163 step 2 diet, advantages of, 54 Angiotensin-converting enzyme inhibitors (ACE inhibitors) for cardiovascular disease prevention, 210212 for managing hypertension and reducing incidence of diabetes type 2, 207208 Angiotensin II receptor blockers (ARBs), to manage hypertension, cardiovascular effects of, 210213 Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), comparison of beta-blockers and

thiazides with amlodipine and perindopril, 215 Anorexia, in patients taking metformin, 190 Anticoagulants, protein C and protein S as, 58 Apolipoprotein-Related Mortality Risk (AMORIS), association of the ApoB/ApoA ratio with myocardial infarction, 140 Apolipoproteins A, biosynthesis of, and insulin resistance, 31 B, and atherosclerosis, 32 E effects of variants on cholesterol levels, 85 role in concentration of dense low-density lipoprotein, 88 Apoptosis antiapoptotic effect of insulin, 11 endothelial cell, stimulation by C-reactive protein, 39 Appetite suppressants, for managing obesity, 176177 Arginine, effect of, on C-reactive protein levels, 165 Assessment, of metabolic syndrome in children and adolescents, 226227 Atherogenesis, with normal low-density lipoprotein cholesterol levels, 108109 Atherogenic lipoprotein phenotype (ALP),

INDEX

237

formation in response to hypertriglycidemia, 33 Atherosclerotic cardiovascular disease. See Cardiovascular disease Atkins diet, major component percentages in, 159160 Atorvastatin, comparison with simvastatin, 187188 Autonomic nervous system, effect on, of weight loss, 173 Beta-blockers effect on glucose tolerance, 209 for managing newly diagnosed hypertension, 215 Beta-cell dysfunction, and oxidative stress, 7677 Binge drinking, effects of, on mortality, 167168 Biological effects, novel, of insulin, 911 Blood glucose, levels of, suppression by insulin, 7 Blood pressure classification of, 208209 effect of sibutramine on decrease in with weight loss, 177178 history of, from age three, 227 See also Hypertension Body mass index (BMI) calculation of, 171172 goal in weight loss to manage dyslipidemia, 181 levels associated with postprandial hyperinsulinemia, 93

Bogalusa Study, on obesity in childhood as a risk factor for cardiovascular disease, 227229 Brain, GLUT-4 of, 103 British Heart Foundation Research Group, on risk factors for coronary heart disease, 47 British Heart Study, algorithm for treating hypertension, 214 British Regional Heart Study, on the effect of exercise on mortality rates, 170 Brown adipose tissue (BAT), 40 Calcium-channel blockers (CCBs), for managing hypertension, 209 age and race considerations, 215 Calorie intake, excessive, relationship with metabolic syndrome in children and adolescents, 226 Calpain 10 gene, effect on risk of diabetes type 2, 85 Captopril Prevention Project (CAPP), comparison of diabetes type 2 incidence, captopril versus other drugs, 207208 Carbohydrate metabolism, enzymes and steps affected by insulin, 9697

238

INDEX

Carbohydrates digestion and absorption of, 199200 effect of lowering dietary consumption of, 162163 Cardiovascular disease (CVD) activity to reduce the rate of, 170 in children and adolescents, 227229 evidence for prediction of, from metabolic syndrome diagnosis, 131136 incidence of, by component of the metabolic syndrome, 138 prediction of, from prediabetes, 68 relationship with circulating methylarginine levels, 67 relationship with diagnosis of metabolic syndrome, 125126 risk factors for, 21, 127128 apoprotein E4, 85 and diagnosis of metabolic syndrome, 128129 postprandial hyperglycemia, 109110 Cardiovascular events effects of body mass index and waist circumference on, 172 mortality, impaired glucose tolerance as a risk factor for, 7071 prevalence of, halting a trial of beta-blockers for hypertension, 215 reduction of by metformin, 190 trials of fibrates to reduce the incidence of, 185

risk of, diabetes type 2 associated with, 227 Cardiovascular system, effect on, of weight loss, 173 Carnitine palmitoyl transferase-1 (CPT-1), role in free fatty acid biosynthesis, 102 Catecholamine, as a lipolytic agent, 97 Centers for Disease Control and Prevention (CDC), on defining obesity from body mass index, 230 Chemokines, expression in adipose tissue, 48 Cholesterol, effects of rimonabant on levels of, 179. See also Apolipoproteins; Lipoproteins Cholesterol absorption inhibitors, to reduce low-density lipoprotein cholesterol, 189 Cholesterol and Recurrent Events (CARE) trial, 141 Chronic kidney disease (CKD), association with cardiovascular disease, 7172 Chylomicron remnant metabolism, effect of insulin resistance on, 3233 Chylomicrons, presentation of free fatty acids to adipocytes by, 106 c-Jun amino terminal kinase (JNK-1) activity of, relationship with obesity, 2930 role in inducing serine phosphorylation of

INDEX

239

insulin receptor substrate-1, 52 Classification, of obesity, 2627 Clinical diagnosis of metabolic syndrome, 115130 Clinical management, of metabolic syndrome, 154223 Coagulation factors, increase of, in obesity, 4849 Collaborative Atorvastatin Diabetes Study (CARDS), effect on incidence of myocardial infarction in diabetes type 2, 188 Compartments, of fat, metabolic differences among, 2627 Contraindications to -glucosidase inhibitor use, 200 to meglitinide use, 203 to metformin use, 191 to rimonabant use, 179 to sibutramine use, 177178 Copenhagen Male Study, on cardiovascular disease risk in hypertension, 66 Coronary artery disease (CAD) benefits of activity to reduce the rate of, 170 metabolic abnormalities associated with, 24 plasminogen activator inhibitor-1 as a risk factor for, 61 role of nuclear factor-B in development of, 99 Coronary Artery Risk Development in Young Adults (CARDIA) study, on dairy products in the

diet, and metabolic syndrome, 232 Coronary heart disease (CHD) association with factors involved in fibrinolysis, 59 effects of diet on, 159160 risk of, in women with polycystic ovary syndrome, 148 See also Cardiovascular disease; Coronary artery disease Correlation coefficient, between body mass index and waist circumference, 137 C-reactive protein (CRP) effect of arginine-rich foods on levels of, 165 as an independent risk factor, for insulin resistance, 132 as an inflammatory marker, 3840 link with cardiovascular disease, 128129, 132133 link with diet, 160 link with insulin resistance, 37 link with polycystic ovary syndrome, 147 reduction in plasma level by thiazolidinediones, 196197, 199 Cushing syndrome, similarities with metabolic syndrome, 110111 Cytokines, role in pathophysiology of metabolic syndrome, 92 Dallas Heart Study, prevalence of nonalcoholic fatty liver disease as measured in, 144

240

INDEX

Danish twin register, on risk factors for insulin resistance, 2425 Data, on worldwide prevalence of metabolic syndrome, 3 DESIR Cohort Study, on nucleotide polymorphism in development of metabolic syndrome, 51 Diabetes altered metabolic states associated with, 25 association with metabolic syndrome, 2, 131136 in children and adolescents, 229 diagnostic criteria for, 69 drugs to manage, 189196 effect of weight loss on onset of, 172 endothelial dysfunction in first-degree relatives of patients, 64 inflammatory markers predicting development of, 5051 nonalcoholic fatty liver disease in families of patients, 142 polycystic ovary syndrome as a risk factor for, 146 precipitation of onset by beta-blockers, 214216 preventing with treatment of the metabolic syndrome, 158 Diabetes Atherosclerosis Intervention Study (DAIS), effect of fenofibrate in diabetes type 2, 185

Diabetes Epidemiology Collaborative Analysis of Diagnostic Criteria in Europe (DECODE) association between two-hour postglucose challenge level, and mortality, 109110 risks to nondiabetic individuals with metabolic syndrome, of death, 134 Diabetes Prevention Program (DPP), on managing impaired glucose tolerance, 206207 Diabetes Prevention Study (DPS), Finland, effect of impaired glucose tolerance management, 207 Diacylglycerol (DAG), change in intracellular concentration of in insulin resistance development, 9899 Diagnosis criteria for metabolic syndrome, 2223 of nonalcoholic fatty liver disease, 142 Diet components of food important in treating obesity, 173176 low-glycemic index, 164 management of, 158168 and prevalence of metabolic syndrome, 5 See also Nutrition Diet and Reinfarction Trial (DART), evaluation of fatty fish consumption

INDEX

241

after a myocardial infarction, 167 Dietary Approaches to Stop Hypertension (DASH) diet, emphases in, 167 Diuretics, for managing hypertension, 209 DNA damage, in oxidative stress, 76 Drugs lipid-lowering, dosages of, 183 for lowering blood cholesterol levels in children, 231232 oral antidiabetic, list and dosages, 192 for treating cardiovascular disease, 156158 for treating metabolic syndrome, 156 Dyslipidemia effect of weight loss on, 173 gene variants regulating, 87 guidelines for managing, 180181 as an independent risk factor for cardiovascular disease, 137138 insulin resistance associated with, 8687 insulin resistance caused by, 16, 3036 as a monogenic disorder, 84 Edinburgh Artery Study, on peripheral vascular disease, 216 Effector defects, in insulin signaling pathways, 16 Endoplasmic reticulum (ER) role in insulin resistance, 99100 stress of, role in insulin resistance, 143144

Endothelial dysfunction (ED) association of with atherosclerosis, 139 with oxidative stress, 6064 with polycystic ovary syndrome, 147 C-reactive protein as a mediator of, 3840 effects of thiazolidinediones on, 196197 pathophysiology of, 6164 Endothelial function, adiponectin as a mediator of, 4647 Endothelial nitric oxide synthase (eNOS), effect of statins on, 187 Energy-deficit diet, description of, 174175 Energy density of a food, defined, 165 Energy intake, restricted, and insulin resistance in the elderly, 74 Estrogen/Progesterone Replacement Study, on incidence of diabetes in treatment groups, 208 Ethnicity, and metabolic syndrome, 5 European Group for the Study of Insulin Resistance (EGSIR) diagnostic criteria suggested by, 122123 on prevalence of metabolic syndrome, 3 on risk factors for insulin resistance, 2425 obesity, 137 Evaluation, predictive information from metabolic syndrome diagnosis, 135

242

INDEX

Exercise, benefits of, 169170. See also Physical activity Expert Panel on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults, calorie intake recommendations of, 174175 Ezetimibe, cholesterol absorption inhibitor, use combined with statins, 189 Family history, to assess risk of metabolic syndrome for children and adolescents, 227 Fats, role in diets to reduce risk of coronary heart disease, 160161 Fatty acid binding protein (FABP) alteration in obesity and diabetes type 2, 108 role in transport of fatty acids to the endoplasmic reticulum, 8788 Fatty acids diversion from adipose tissue to nonadipose tissue, 107 unsaturated, benefits of replacing saturated fatty acids with, 161 -3, to prevent coronary heart disease, 159160 See also Free fatty acids Fatty liver disease, nonalcoholic, in metabolic syndrome, 141146

Fetal glycolated hemoglobin (FGH), association with birth weight, 19 Fiber, dietary, protective effects of, 164165 Fibrates, role in treating metabolic syndrome, 183186 Fibrin, role in fibrinolysis, 5759 Fibrinogen correlation with cardiovascular disease risk factors, 128 increase of, in obesity, 4849 and insulin resistance, 5960 role in pathophysiology of metabolic syndrome, 92 Fibrinolysis, reactions of, 5759 Fish, effect on cardiovascular risk factors, 162 Formulations, of sulfonylureas, 202 Framingham Heart Study algorithm for estimating risk of cardiovascular disease, 155 on increase in small lowdensity lipoprotein particles, 34 on risk factors for cardiovascular disease, 135136 high-density lipoprotein cholesterol, 137 relationship to metabolic syndrome, 126 on risk factors for diabetes type 2, 135136 risk score from, as a predictor of cardiovascular disease, 129, 132

INDEX

243

Framingham Offspring Study C-reactive protein as a predictor of cardiovascular disease in, 39 on subclinical coronary atherosclerosis risk factors, 136 Free fatty acid (FFA) abnormalities of, in the metabolic syndrome, 105109 effects of overproduction of, 8990 effects on insulin action and secretion, 70 esterification of, adipose tissue uptake in, 106 hepatic uptake of, relationship with visceral fat, 27 as the major factor in insulin resistance development, 97100 oxidation of, causing insulin resistance in the obese, 9597 reduction of levels of, by thiazolidinediones, 193 role in pathogenesis of metabolic syndrome, 98101 role in pathophysiology of metabolic syndrome, 91 Gemfibrozil, studies of effects on cardiovascular event rate, 185 Gender and free fatty acid release postprandially, 93 and prevalence of metabolic syndrome, 45

Genes apM1, adiponectin as the product of, 45 calpain 10, effect on risk of diabetes type 2, 85 GEK effect of mutations and variants in, 86 mutations causing MODY, 86 HNF4, association with diabetes, 86 HNFI, association with diabetes type 2 and MODY, 86 ob, obese, leptin as the product of, 1619, 4244 PPAR-2, association with insulin resistance and risk of type 2 diabetes, 84 role in the mechanism of the metabolic syndrome, 8386 variants altering the risk of metabolic syndrome, 8587 variants associated with dyslipidemia and insulin resistance, 86 Genetic factors in metabolic syndrome, 5 in severe insulin resistance, 1516 thrifty genotype hypothesis in insulin resistance, 17 Glimepiride, to control hyperglycemia, 202 Glinides, hypoglycemic effect of, 204 Glipizide, to control hyperglycemia, 202 Glucocentric view, of insulin resistance, 9597

244

INDEX

Glucocorticoid hormones involvement in metabolic syndrome, 110111 relationship with cardiovascular mortality, 49 Glucocorticoid receptor (GR), association of polymorphisms with metabolic syndrome, 8485, 111 Glucokinase (GCK), mutations in the gene for, causing MODY, 86 Gluconeogenesis, pathway of, 1213 Glucoprotein PC-1, potential role in insulin resistance and diabetes type 2, 86 Glucose disposal of, by skeletal muscle, 8 muscle, insulin resistance and metabolism of, 100101 plasma, role in pathophysiology of metabolic syndrome, 91 stimulation of reactive oxygen species by, 5354 Glucose-6-phosphatase, induction of, and free fatty acid levels, 102 Glucose homeostasis, role of insulin in, 7 Glucose intolerance as a diagnostic criterion for metabolic syndrome, 124128 in hypertensives, 66 link with insulin resistance, 6771 Glucose tolerance, effect of beta-blockers on, 209

-Glucosidase inhibitors combination with sulfonylureas, 206 effect on absorption of polysaccharides and disaccharides, 199200 GLUT-4 glucose transporters, 13 stimulation by insulin, 8 Glyburide, to control hyperglycemia, 202 Glycemia, postprandial, importance of, 109110 Glycemic index controlling in a diet to reduce obesity, 176 of selected foods, 164 Glycemic load, defined, 165 Glycoproteins, insulin receptor, 1115 Goals, of clinical management of the metabolic syndrome, 156158 Growth hormones, role in metabolic syndrome, 110111 Gruppo Italiano per lo Studio della Sopravvivenza nellInfart Miocardio (GISSI), on the effects of omega-3 fatty acid supplementation, 166 Harris-Benedict equation, for calculating daily calorie intake, 174 Helsinki Heart Study (HHS), effect of gemfibrozil on cardiovascular event incidence, 185 Hemoglobin A1c, postprandial glycemia contribution to, 109110 Hemostatic mechanism, and insulin resistance, 6061

INDEX

245

Hepatic glucose, production of, 78 Hepatic hormone, insulin as, in the fasting state, 7 Hepatic insulin resistance, induction of, 104105 Hepatic lipase, regulation of high-density lipoprotein cholesterol by, 87 Hepatic steatosis, insulin resistance due to, mechanism, 99100 Hepatocyte nuclear factor-1 (HNF-1) gene association with diabetes type 2 and MODY, 86 Hepatocyte nuclear factor-4 (HNF-4) gene, association with diabetes type 2 and MODY, 86 High-density lipoprotein (HDL) apolipoproteins of, 3536 levels of effect of nicotinic acid on, 182183 due to fibrate effects, 184 in insulin resistance, 3031 as a risk factor for coronary heart disease, 137 relationship with insulin resistance, 3031 High-density Lipoprotein Intervention Trial (HIT), on raising high-density lipoprotein cholesterol, to reduce cardiovascular risk, 185 Homeostasis model assessment (HOMA) relationship between hypertension and insulin resistance, 6465 on the relationship between insulin resistance and

nonalcoholic fatty liver disease, 143 on the relationship between insulin resistance and obesity, 6 Hormone replacement therapy (HRT), value for managing diabetes, 208 Hormone-sensitive lipase (hsL), effect of tumor necrosis factor- on, 41 Hypercholesterolemia, isolated, fibrate drugs for managing, 184 Hyperglycemia endothelial dysfunction promotion by, 6364 insulin resistance caused by, 16 Hyperinsulinemia association with atherosclerosis, 139 in hypertensives, 66 leading to increased sympathetic nervous system activity, 65 possible role of insulininduced insulin resistance in, 12 See also Insulin resistance Hyperlipidemia, pravastatin for managing, 208 Hypertension comparison among drugs for managing, for incidence of diabetes, 207208 disorders involving, as monogenetic syndromes, 84 induction of endothelial dysfunction by, 63 link to insulin resistance, 6467

246

INDEX

Hypertriglyceridemia fibrates for managing, 184 mechanism of, 103109 relationship with small dense low-density lipoprotein particles, 3435 Hyperuricemia, association with insulin resistance, 75 Impaired fasting glucose (IFG), association with risk of diabetes, 68, 132 Impaired glucose tolerance (IGT) management of, 206207 prediction from of diabetes, 132 of insulin resistance, 6771 and prevalence of metabolic syndrome, 2 Inflammation induction of insulin resistance by, 93 in polycystic ovary syndrome, 147 Inflammatory hypothesis, relating inflammation and insulin resistance, 4950, 5153 Inflammatory mediators, effect of insulin on, 910 Insulin blood levels of, 7 combination with thiazolidinedione, 205 impaired action of, 1516 normal action of, 619 Insulin receptor defined, 1112 insulin resistance due to alterations in, 1516 subunit serine/threonine phosphorylation of, 1213

Insulin receptor substrates (IRS) relationship with insulin resistance and diabetes type 2, 8687 relationship with insulin resistance and nonalcoholic steatohepatitis, 144 role in regulating low-density lipoprotein particle size, 89 Insulin resistance angiotensin-converting enzyme inhibitors for managing related conditions, 212213 association of with atherosclerosis, 139 with dyslipidemia and gene variants, 8689 with excess adiposity, 137 with the inflammatory mechanism, 36 with risk of chronic kidney disease, 72 characteristics predisposing individuals to, 116117 in children and adolescents, 226 as a component of metabolic syndrome, 2326 relative importance of, 8992 effect of defective leptin action on, 4244 endothelial dysfunction due to, 62 fat accumulation in the liver associated with, 141 fatty acid-induced, mechanism of, 101102 historical designation of metabolic syndrome as, 1

INDEX

247

an inflammatory hypothesis, 5153 possible pathway leading to, 9091 primary, relationship with obesity, 93 reversal by adiponectin, 46 role of in hypertension, 6667 in pathogenesis of nonalcoholic steatohepatitis, 143144 type A, characteristics of, 89 and weight loss, 172 Insulin Resistance Atherosclerosis Study, adipokine levels related to insulin resistance in, 53 Insulin sensitivity, relationship of with dietary fat, 161162 with visceral adiposity, 9294 Interleukin-6 (IL-6), link with insulin resistance, 37 International Diabetes Federation (IDF) criteria for diagnosing metabolic syndrome, 118120 definition of metabolic syndrome, 2 International Diabetic Trial (INDT), comparison of irbesartan and amlodipine for managing renal disease, 213 Intramyocellular lipids (IMCLs), correlation with insulin resistance, 98 Intramyocellular triglyceride (IMTG), accumulation of, association with muscle insulin resistance, 107108

Islets of Langerhans, insulin secretion by cells of, 7 Joint British Societies, algorithm for estimating risk of cardiovascular disease, 155 Jupiter trial, relating C-reactive protein levels with vascular survival, 39 Kir 6.2 gene, relationship with diabetes type 2, 8586 Kuopio Ischemic Heart Disease Risk Factors (KIHD) study, on C-reactive protein levels and risk of metabolic syndrome, 5051 Lamin A/C, mutations of, effects on low-density lipoprotein particle size, 89 Left ventricular hypertrophy (LVH), in young patients with essential hypertension, 229 Leprechaunism, characterization of, 88 Leptin correlation with subcutaneous fat levels, 29 dephosphorylation of insulin receptor substrate-1 by, 144 gene for, treating severe obesity associated with, 84 resistance to during aging, 74 insulin signaling defects due to, 4344 role in fat metabolism, 4244

248

INDEX

Leucocyte chemotaxis, effect of thiazolidinediones on, 197198 Lifestyle modification, for reducing the risk of cardiovascular disease, 154, 156 Lifetime risk of diabetes, in the United States, 68 Lipase, hormone-sensitive, regulation of free fatty acid release from adipose tissue by, 105 Lipidemia, postprandial, significance of, 3233 Lipids abnormalities of, in polycystic ovary syndrome, 147 effects on of metformin, 190 of nicotinic acid, 182183 of particle size and atherogenicity, 3334 in skeletal muscle and liver, mechanism of accumulation, 101103 Lipocentric view, of the development of insulin resistance, 9798 Lipodystrophic syndromes, leptin deficiency in, 44 Lipodystrophy, defined, 88 Lipogenesis, de novo, in liver, 104 Lipolysis defined, 97 effect of insulin on, 911 factors affecting the rate of, 9293 promotion of, by tumor necrosis factor-, 52, 9394

role in pathophysiology of metabolic syndrome, 91 Lipoprotein lipase pathway (LPL pathway), regulation of triglycerides in tissues in, 97 Lipoproteins, remnant, 3233. See also Apolipoproteins; High-density lipoproteins; Very low-density lipoproteins Lipotoxicity, of free fatty acids for cells, 70 Liver C-reactive protein production of, 3840 effect in of adiponectin, 45 of free fatty acids, 100 fatty, link to insulin resistance, 29, 141146 glucose production control in, 102 metabolism of sulfonylureas in, 201202 as a target for cytokine action, 4849 Losartan Intervention for Endpoint (LIFE) study, comparison of drugs for hypertension, reduced incidence of diabetes type 2, 208 Low birth weight, association with metabolic syndrome in adulthood, 1719 Low-density lipoprotein effect of rimonabant on, 179 particle size gene variants regulating, 8889 and risk of coronary heart disease, 139140

INDEX

249

and risk of cardiovascular disease, 3132 small, dense, 3435 Low-density lipoprotein cholesterol, effect of statins on, list, 187188 Lower-body fat, study of metabolic activity in, 2728 Lyon Diet Heart Study evaluation of the Mediterranean diet, 166 of -linolenic acid, effect on coronary mortality, 161 Macronutrients in a diet for managing obesity, 175176 inflammation induced by, 5356 Macrophage migration inhibitor factor (MIF), effect of insulin on levels of, 9 Malnutrition, fetal, effect on insulin resistance and metabolic syndrome, 1819 Markers inflammatory effect of weight loss on, 173 as predictors of metabolic syndrome, 5051 of nonalcoholic fatty liver disease, relationship with metabolic syndrome, 142 Maturity onset diabetes of the young (MODY), as a monogenetic disorder, 84 Mechanisms, of insulin resistance, 2526 related to hypertension, 65

Mediterranean diet, content and effects on cardiovascular risks, 166 Meglitinides, stimulation of insulin secretion by, 203206 Metabolic equivalents (METs), for measuring the rate of energy expenditure in exercise, 169 Metabolic risk factors managing, 180217 predisposing to atherosclerotic disease, 2122 Metabolic syndrome components of, 2182 defined, 21 Metformin combination of with nateglinide, 205 with sulfonylurea, 204205 with thiazolidinedione, 205 effect of on lipid accumulation in the liver, 145 on metabolic syndrome, 189191 on metabolic syndrome prevalence in women with polycystic ovary syndrome, 148149 on plasma concentration of macrophage migration inhibitor factor, 11 on reduction of plasminogen activator inhibitor-1 levels by, 61 as a treatment for nonalcoholic steatohepatitis, 145146

250

INDEX

Methylarginine (MA), circulating levels of, relationship with endothelial dysfunction, 67 Mexico City Diabetes Study, on C-reactive protein as a predictor of metabolic syndrome, 3840 Microalbuminuria, association with chronic kidney disease, 7172 Micronutrients, insulin resistance caused by, 56 Miglitol, for managing carbohydrate levels in diabetes type 2, 199200 Mitochondrial oxidative phosphorylation, defective, relating to triglyceride accumulation in muscle, 99100 Mitogen-activate protein (MAP) kinase, in an insulin signaling pathway, 11 Mitogenic pathway, 62 Monogenic components, of metabolic syndrome, 84 Mononuclear cells (MNCs), proinflammatory changes in due to macronutrient intake, 54 in obesity, 56 Montana diet, glycemic index of carbohydrates in, 164 Multiple Risk Factor Intervention Trial (MRFIT), on risk factors for coronary heart disease, and mortality rate, 137

Muscatine Study, on obesity in childhood as a risk factor for cardiovascular disease, 227228 Muscle, effect of adiponectin in, 45 Mutations, in the PPAR- gene, effects of, 84 Myocardial infarction (MI) association with metabolic syndrome, 133 reduction in the rate of, gemfibrozil trial, 185 Myocardium, glucose uptake in diabetes, 94 Myopathy, as a side effect of statins, 188 Nateglinide combination with metformin, 205 for managing hyperglycemia, 204 National Cholesterol Education Program (NCEP) Adult Treatment Panel of, 1 on clinical diagnosis of metabolic syndrome, 115118 list of components of metabolic syndrome, 21 guidelines for treating hyperlipidemia, 157 guidelines for treatment of hyperlipidemia, 157 See also Adult Treatment Panel III National Health and Nutrition Examination Survey (NHANES) on C-reactive protein levels by ethnicity, 39

INDEX

251

cross-sectional data analysis from, prevalence of coronary heart disease in, 134 on pitfalls of criteria for diagnosing metabolic syndrome, 127, 133 on prevalence of metabolic syndrome, 2 on prevalence of metabolic syndrome in children and adults, 225 on relationships between chronic kidney disease and cardiovascular disease, 7172 on validity of tests for insulin resistance, 71 National Heart, Lung, and Blood Institute (NHLBI), on causes of metabolic syndrome, 120 National Institute of Clinical Excellence (NICE), study comparing betablockers and thiazide with amlodipine and perindopril, 215 National Institutes of Health, Obesity Clinical Guidelines for defining metabolic syndrome, 115118 Nicotinic acid (niacin), role in treating metabolic syndrome, 181183 Nitric oxide (NO) effect of C-reactive protein on release of, 3839 effect of hyperlipidemia on the bioavailability of, 187 effect of statins on expression of, 187188 effect on production of

epithelial, role of adiponectin, 46 by thiazolidinediones, 197 release from the endothelium, 6264 in a signaling pathway stimulating glucose uptake in muscle, 1315 Nonalcoholic steatohepatitis (NASH), 141146 Nonesterified fatty acids (NEFAs) production of, in insulin resistance, 143 role in insulin resistance, 97 Non-insulin-dependent diabetes mellitus (NIDDM), link to essential hypertension and cardiovascular heart disease, 2324 Nuclear factor-B signaling pathway, 46 activation of, 99 Nuclear magnetic resonance (NMR) spectroscopy, measurement of intramyocellular lipids using, 98 Nurses Health Study, on effect of fats on risk of coronary heart disease, 160161 Nutrient restriction, to reverse leptin resistance, 44 Nutrition diets to manage diabetes and cardiovascular disease, 158168 effect of low-fat diets on triglyceride levels, 35 hypertriglyceridemic effect of a high-sucrose diet, in apoprotein E carriers, 85

252

INDEX

Nutrition (continued) role in development of type 2 diabetes, 1718 Nuts, effect of consumption on coronary heart disease risk, 165166 Obesity abdominal, as a risk factor for chronic renal disease, 72 association of with a chronic inflammatory response, 52 with fatty liver, 142 with nonalcoholic steatohepatitis, 144 as a cause of insulin resistance, 5152 in childhood relationship with adult-type obesity, 231232 relationship with metabolic syndrome, 229231 coagulation risk from, 59 and hypertension, 6465 managing, factors important in, 173174 massive, and metabolic syndrome, 107 measures of, 120, 171172 relationship of with inflammation, 3637 with insulin resistance, 25 with metabolic syndrome, 56, 17, 21, 9294, 124, 136141 with metabolic syndrome, in children and adolescents, 224234 with polycystic ovary syndrome, 147148

with tumor necrosis factor-, 41 as a risk factor for insulin resistance, 2630 simple gene mutations associated with, 84 as a target in management of metabolic syndrome, 156 visceral adiponectin level associated with, 47 metabolic abnormalities associated with, 2829 See also Body mass index; Waist circumference Obstructive sleep apnea (OSA), association with cardiovascular disease, 149150 Olanzapine, increase in risk of metabolic syndrome with use of, 6 Oral glucose tolerance test (OGT test) identification of individuals at high risk for diabetes from, 132133 inclusion in diagnostic criteria for metabolic syndrome, 118 Orlistat effects on diabetes risk in obese subjects, 149 effects on metabolic risk factors, 158 as a gastrointestinal lipase inhibitor, to reduce absorption of dietary fat, 178179 Oxidative stress endothelial dysfunction associated with, prediction of

INDEX

253

cardiovascular disease from, 62 link with insulin resistance and cardiovascular disease, 7577 macronutrient intake as a regulator of, 5556 and pathogenesis of insulin resistance, 100 and pathogenesis of nonalcoholic steatohepatitis, 144 See also Reactive oxygen species p21ras, switch element in insulin signaling, 13 p85, M3261 polymorphism of, low-density lipoprotein particle size in, 89 Pancreatic cells, effect of sulfonylureas on, 201202 Pathogenesis of metabolic syndrome, 83114 in children and adolescents, 225226 prothrombotic state components related to, 6061 of nonalcoholic steatohepatitis, 142143 Pathophysiology, of metabolic syndrome, 8992 Peripheral insulin resistance, effects of protein tyrosine phosphatases on, 12 Peripheral vascular disease (PVD), risk factors for, 216217 Peroxisome proliferationactivated receptor- (PPAR- agonist, effects

of, in preventing atherosclerosis, 195196 Peroxisome proliferationactivated receptor- (PPAR-), effects of, in women with polycystic ovary syndrome, 149 Peroxisome proliferationactivated receptor-2 (PPAR-2 link with insulin resistance and dyslipidemia, 84 P115Q mutation, features of, 89 regulation of lipid homeostasis by, 198 variants affecting specific components of metabolic syndrome, 87 Pharmacological agents, role in treating nonalcoholic steatohepatitis, 145146 Pharmacotherapy, for managing obesity, 176180 Phenotype hypothesis, link with low birth weight and metabolic syndrome, 1619 Phosphatidylinositol-3-kinase, activation of, in glucose transport regulation, 11 Phosphoenolpyruvate carboxykinase (PEPCK), repression of, by insulin, 1213 3-Phosphoinositides, downstream effectors of, 13 Phosphoinositol-3-kinase (PI-3 kinase), activity of, in insulin-stimulated glucose uptake, 13

254

INDEX

Physical activity in children and adolescents, to prevent cardiovascular disease, 232 defined, 168 effects on metabolic syndrome, 168172 and prevalence of metabolic syndrome, 5, 7374 reduced, relationship with metabolic syndrome in children and adolescents, 226 Physical fitness, and insulin resistance, 25 Physicians Health Study, on low-density lipoprotein particle size as a risk factor from heart disease, 140 Pioglitazone, effect on blood pressure, 193195 Plaque development effect of thiazolidinediones on, 198199 role of C-reactive protein in, 50 Plasma-cell differentiation factor-1 (PC-1), polymorphism of, lowdensity lipoprotein particle size in, 89 Plasminogen activator inhibitor-1 (PAI-1) correlation with cardiovascular disease risk factors, 128 decrease of, with metformin administration, 190 increase of, in obesity, 4849 as a marker for premature cardiovascular disease, 139 sources and effects of, 6061

Platelets, aggregation of, in insulin resistance, 60 Pleiotropic effects, of statins, 186188 Polycystic ovary syndrome, association with metabolic syndrome, 146148 Polygenic diseases, related to metabolic syndrome, 84 Polyunsaturated fatty acids (PUFAs), and serum levels of inflammatory markers, 160 Positron emission tomography (PET), studies indicating change in glucose uptake in the myocardium in diabetes, 94 Postprandial glycemia, as a marker for insulin resistance, 110 Postreceptor defects, in impaired insulin action, 1516 Pravastatin, for managing hyperlipidemia, 208 Prediabetes and cardiovascular disease prediction, 68 managing, 206 Prereceptor/receptor defects, in impaired insulin action, 1516 Prevalence of insulin resistance, specific groups at risk, 83 of metabolic syndrome, 16 in children and adolescents, 225 of metabolic syndrome in the general population, 2 Proinflammatory cells, plasma, role in pathophysiology

INDEX

255

of metabolic syndrome, 91 Proinflammatory state, 3656 role in pathophysiology of metabolic syndrome, 92 Prospective Cardiovascular Munster (PROCAM) study algorithm for estimating risk of cardiovascular disease, 155 on coronary heart disease risk factors, 137, 155156 Prospective Pioglitazone Clinical Trial in Macro Vascular Events (PROACTIVE), decrease of cardiovascular events in, 193194 Protein kinase B (serine/threonine kinase Akt) activity in insulin-stimulated glucose uptake, 13 effect of suppressor of cytokine signaling-3 on, 53 Protein kinase C (PKC), role in peripheral insulin resistance, 12 Protein Power diet, major component percentages in, 159160 Prothrombotic state, role in pathogenesis of metabolic syndrome, 5761 Pseudoacromegaly, low-density lipoprotein particle size in, 89 Quebec Cardiovascular Study on low-density lipoprotein particle size, and

ischemic heart disease, 139140 on screening tools for identifying men at high risk of coronary heart disease, 155 Quebec Family Cohort Study, criteria for diagnosing metabolic syndrome in children and adolescents, 224 Rabson-Mendenhall syndrome, description of, 89 Ramipril, association of use with reduced incidence of diabetes, 207208 Randle glucose-fatty acid cycle, disruption of glucose homeostasis via, 9597 Random controlled trial (RCT), of sibutramine alone or with behavior therapy and dietary therapy, 177178 Reactive oxygen species (ROS) sensitivity of cells to, 7677 suppression by insulin, 1011 Relative risk, of diabetes, in individuals diagnosed with metabolic syndrome, 132 Remnant-like particles (RLPs), cholesterol and triglyceride, in diabetic individuals, 140 Rennin-angiotensin-aldosterone system (RAAS), effect on, of insulin resistance, 212213 Repaglinide combination with thiazolidinedione, 205 for managing postprandial hyperglycemia, 203204

256

INDEX

Resistin, link among obesity, insulin resistance, and type 2 diabetes, 47 Rimonabant, effect on weight loss, 158, 179180 Risk factors, for cardiovascular disease, 2122 management of, 158180 Rosiglitazone effect of insulin sensitizers of, antiinflammatory, 11 effect on blood pressure, 194195 effect on nonalcoholic steatohepatitis, 145 San Antonio Study, comparisons of criteria for predicting cardiovascular disease, 131134 Scandinavian Simvastatin Survival Study (4S), reduction of cardiovascular disease in, 157158 Secretogogues, for managing hyperglycemia, 201202 Sibutramine as an adjunct for treating obesity, 177178 effect on metabolic risk factors, 158 Side effects of angiotensin-converting enzyme inhibitors, 211212 of fibrates, 185186 of -glucosidase inhibitors, 200 of metformin, 191 of nicotinic acid, 182183 of orlistat, 178179 of sibutramine, 177178

of statins, 188 of sulfonylureas, hypoglycemia, 202 of thiazides, 215216 Signaling, by adiponectin, net effects of, 45 Signaling cascade, intracellular, for insulin, 1115 Simvastatin, effect of combination with nicotinic acid, 182183 Skeletal muscle abnormal fatty-acid metabolism in, 107 fractional extraction of free fatty acids in, 108 Sleep apnea, relationship with cardiovascular disease, 149150 Smoking association with metabolic syndrome among overweight adolescents, 7273 effect of exercise on cessation of, 171 effect of rimonabant on cessation of, 179180 as a risk factor in peripheral vascular disease, 216 South Beach diet, percentages of major components of, 164 Soya, effect of consumption on cholesterol levels, 163 Statins, effects on cholesterol levels, 186189 Stenols, plant, effect on cholesterol levels, 163 Steroids, relationship with Cushing syndrome, 49 Sterol regulatory elementbinding protein 1c

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257

(SREBP1c), role in lipogenesis in muscle and liver, 102 Sterol regulatory elementbinding proteins (SREBPs), role in pathogenesis of nonalcoholic steatohepatitis, 145 Sterols, plant, effect on cholesterol levels, 163 Stillman Diet, major component percentages in, 159160 Stress, endoplasmic reticulum, role in insulin resistance, 99100 Stroke association with metabolic syndrome, 133 reduction in the rate of atorvastatin trial, 188 gemfibrozil trial, 185 Sugar Busters diet, percentages of major components of, 164 Sulfonylurea receptor I (SURI) effects of drugs binding to, in diabetes-related disorders, 201202 and susceptibility to diabetes, 8586 Sulfonylureas combination with -glucosidase inhibitors, 206 combination with metformin, 204205 combination with thiazolidinedione, 205 for managing hyperglycemia, 201202 similarity to metformin in effects, 190

Suppressor of cytokine signaling-3 (SOC-3), 4243 effect on tyrosine phosphorylation of the insulin receptor, 5253 Surgery, to manage obesity, 180 Susceptibility, endogenous metabolic, for metabolic syndrome, 21 Swedish Obese Subjects (SOS) study, of surgery to manage weight loss, effect on diabetes type 2 incidence, 207 Sympathetic nervous system, effect of insulin on, 65 Syndrome, implications of the concept of, 135 Syndrome X, historical designation of metabolic syndrome, 1 Systemic Coronary Risk Evaluation (SCORE), algorithm for estimating risk of cardiovascular disease, 155 Systolic blood pressure, as a determinant of endothelial dysfunction, 63 Tangier disease, low levels of high density lipoprotein cholesterol in, 31 Thiazolidinediones (TZDs) combinations with other drugs, 205 reduction of plasminogen activator inhibitor-1 levels by, 61 for treating insulin resistance, 149

258

INDEX

Thiazolidinediones (TZDs) (continued) for treating insulin resistance and diabetes, 191196 for treating insulin sensitivity, 84 Thrifty genotype hypothesis about evolutionary selection of genes related to insulin resistance, 83 link with low birth weight and metabolic syndrome, 1619 Tissue factor pathway inhibitor (TFPI), role in fibrinolysis, 5859 Tissue plasminogen activator (t-PA), vascular endothelium as a source of, 5758 Torcetrapid, mortality due to, 158 Treatment, of metabolic syndrome and polycystic ovary syndrome, 148149 Triglyceride-rich lipoproteins (TRLs), remnants of, and coronary heart disease, 36 Tumor necrosis factor- (TNF-), role in pathophysiology of metabolic syndrome, 92 Tumor necrosis factor- link with insulin resistance, 37, 41 overexpression by adipose tissue, and nonalcoholic steatohepatitis, 144 Twin studies, of insulin resistance, 83

Two-hit hypothesis, for nonalcoholic steatohepatitis development, 143 Tyrosine kinase, activity of, affecting insulin receptor, 12 Upper-body fat, correlation with insulin resistance, 2627 Urokinase plasminogen activator (u-PA), 58 Validity, of metabolic syndrome as a diagnosis, questions about, 123 Vascular endothelium, as a source of tissue plasminogen activator, 5758 Vascular injury, and atherosclerosis, cellular processes involved in, 6263 Verona Diabetes Complications Study, relative hazard ratio for cardiovascular disease outcomes in, 133 Very low-density lipoproteins (VLDLs) hepatic, relationship with atherogenic dyslipidemia, 3031 increased synthesis of, in hypertriglyceridemia, 103104 presentation of free fatty acids to adipocytes by, 106 Visceral fat, 9293 correlation with insulin resistance, 27

INDEX

259

Vitamin E (-tocopherol), effect on oxidative stress and inflammation, 5455 Voglibose, for managing carbohydrate levels in diabetes type 2, 199200 Waist circumference (WC) measurement of, 171172 as a measure of central obesity, 28 weighting of, as a criterion for metabolic syndrome, 120 Weight gain, with sulfonylurea use, 202 Weight loss benefits of, 172173 effect on histological lesions of nonalcoholic steatohepatitis, 146 Weight management, in metabolic syndrome, 159160 West of Scotland Coronary Prevention Study (WOSCOPS), on leptin levels and risk of coronary heart disease, 44 White adipose tissue (WAT), 40

White cell count, as a predictor of cardiovascular disease, 139 Womens Angiographic Vitamin and Estrogen Trial, prevalence of metabolic syndrome in, 134 Womens Health Study, on risk of diabetes related to C-reactive protein levels, 38 World Health Organization (WHO) clinical criteria for metabolic syndrome, 117118, 127 predictive power of, 131, 134 on prevalence of metabolic syndrome, 2, 5051 Xanical in the Prevention of Diabetes in Obese Subjects (XEN-DOS) study, effects of weight loss accompanying orlistat administration, 178179 Zone diet, major component percentages in, 159160