fasting, intermittent: introduction, xxi, 191; author’s experience with, 216, 17; bariatric surgery as, 191; basal metabolic rate impact, 197, 198; choosing a regimen, 201, 2; comparison with low- carbohydrate, healthy-fat diet, 198, 99; vs. continuous caloric reduction, 192, 95; dawn phenomenon, 203, 4; dumping toxic load, 202; early attempts, 6, 7, 190; effectiveness of, 199, 200; energy expenditure and sources, 52, 198; in Greek Orthodox Church, 72; with medications, 200, 201; results and progress, 202; starvation myth, 196, 98; use of term, 52; wartime food rationing, 191; weight loss from, 197, 98 fasting insulin, 57, 58, 65, 169, 194 fat, abdominal (visceral/ectopic/intra-organic): detection, 41, 43; insulin resistance and, 79, 90, 91; metabolic syndrome and, 108, 113, 14; risk factor for type 2 diabetes, 41, 43; type 2 diabetes reversal from removal of, 171, 72; types, 44 fat, body: creation of, 51, 53, 109; energy manufactured from during fasting, 52, 109, 198; hormonal control of, 47, 54; subcutaneous, 42, 43, 79, 114.
See also de novo lipogenesis; fat, abdominal; hypertriglyceridemia fat, dietary: demonization of, 8, 40, 95; glycemic load, 40; health benefits, xx, xxi, 155, 176, 177, 213, 14; healthy sources, 187; heart disease and, 154; lack of evidence for dangers, 9, 40; metabolism of, 50, 108, 181; saturated, 9, 109, 176; seed and vegetable oils, 187, 88; trans fats, 9, 188.
See also diets fat mass hypothesis, 170, 71 fatty liver: overview, 29, 30, 91, 92; alcohol-related, 80, 81, 99, 100; in animals, 84, 85; cause and development, 71, 79, 83, 84, 85, 113; cirrhosis, 82; diagnosis, 80; fatty pancreas and, 89; from fructose, 84, 99, 104, 186; insulin resistance and, 44, 80, 82, 83, 91; metabolic syndrome and,
116; non-alcoholic fatty liver disease (NAFLD), 29, 30, 81, 83; non-alcoholic steatohepatitis (NASH), 30, 44, 82; prevalence, 82, 83; related diseases, 82; reversibility of, 84; from sucrose, 186 fatty muscle, 85, 86, 91 fatty pancreas, 89, 90, 91 feet: nerve damage, 25, 26; non-healing foot ulcers, 28, 30, 72 Finland, 205 fish, 177 Fleming, Alexander, 61 fois gras, 84, 85 food pyramid, 9, 10, 152 food rationing, 191 food storage.
See de novo lipogenesis (DNL); glycogen foregut hypothesis, 170 Framingham studies, 27, 111 French paradox, 176 Fröhlich, Alfred, 81 fructose: consumption increases, 97, 98; de novo lipogenesis (DNL) from, 109; elimination from diet, 185, 86; fatty liver role, 84, 99, 104, 186; hypertriglyceridemia from, 110, 11; insulin resistance from, 100, 101, 182; metabolism of, 96, 98, 99, 103, 4; molecular structure, 95; sources, 96, 97, 185; toxicity and health risks, 97, 98, 102, 3, 103, 4, 181.
See also high- fructose corn syrup; sugar fruit, 40, 96, 97, 186 Fung, Jason, 211, 12, 214, 15 fungal infections, 30, 31
gastric dumping syndrome, 166, 167 gastric “lap” band, 167 gestational diabetes, 14 ghrelin, 48, 170 glicizide, 141 glipizide, 141 Global Report on Diabetes (WHO), 175 glucagon, 203 glucagon-like peptide 1 (GLP-1) analogs, 148, 149 gluconeogenesis, 52, 54, 87, 144 glucose: metabolism of, 18, 98, 104; molecular structure, 95. See also blood glucose; hyperglycemia; hypoglycemia glucotoxicity: acarbose and, 147; cancer and, 136; DPP-4 inhibitors and, 145; GLP-1 analogs and, 148; medication overview, 148, 49; replacement with insulin toxicity, 125, 26, 130, 31, 134, 136; SGLT2 inhibitors and, 146; sulfonylureas (SUs) and, 141; type 1 diabetes and, 124, 25, 126; type 2 diabetes and, 126, 29, 141 glyburide, 141
glycemic index, 40, 96, 97 glycemic load, 40, 178, 180 glycogen: creation and storage in liver, 51, 79, 98, 104, 109; energy produced from, 52; fasting usage of, 52, 171, 198; in muscles, 51, 85 Golden Years Cohort Study, 130 Greek Orthodox Church, 72 Gregory the Great, 190 growth hormone, 49, 64, 197, 203
Hallberg, Sarah, 151, 163, 172 Hamdy, Osama, 172, 184 Harcombe, Zoë, 40 HDL (high-density lipoproteins), 106, 111, 12, 177 health costs, 12, 139 heart attacks: from atherosclerosis, 22, 26, 27; dietary fat blamed for, 8; healthy fat benefits, 177; high blood pressure and, 114; metabolic syndrome and, 107; metformin benefits, 127; rosiglitazone (Avandia) risks, 142, 43; sulfonylureas (SUs) risks, 141.
See also cardiovascular disease hemoglobin A1C, 16, 17, 127, 135, 36, 140, 146, 156 hepatic cycle, 91, 92.
See also fatty liver hepatic steatosis, 82.
See also fatty liver HFCS (high-fructose corn syrup), 96, 97, 102, 103, 104, 187.
See also fructose high blood pressure (hypertension), 106, 107, 114, 15, 147 high-density lipoproteins (HDL), 106, 111, 12, 177 high-fructose corn syrup (HFCS), 96, 97, 102, 103, 104, 187.
See also fructose high-protein diet, 178, 79 Himsworth, Harold Percival, 7, 8 history, diabetes mellitus: ancient world, 3, 4; beginnings of epidemic, 8, 10; contemporary epidemic, 10, 12; early dietary treatments, 4, 5; early fasting treatments, 6, 7; identification of type 1 and type 2 diabetes, 7, 8; insulin discovery, 7; term origins, 4; understanding of disease, 4, 5 homeostasis, 58, 59, 60, 61.
See also insulin resistance; resistance hope, 211 hormones: blood glucose control, 18; hunger and satiety control, 45, 48; production of, 49; release cycles, 64, 203; resistance, 63; weight regulation, 47, 48, 112, 13 hyperglycemia: beta cell dysfunction and, 88; cardiovascular disease risk, 134; causes, xvi, 123; complications from, 124; definition, 14; health risks from, 133; symptoms, 15; toxicity of, 124, 25, 126; treatment of ineffective for type 2 diabetes, 12, 143.
See also glucotoxicity hyperinsulinemia: atherosclerosis risk, 134; cancer risk, 136, 37; carbohydrate-insulin hypothesis, 54, 55; cardiovascular disease risk, 134, 36; caused by insulin, 129, 30; diabesity caused by, 66; high blood pressure risk, 114, 15; hypertriglyceridemia risk, 111; insulin resistance as defense against, 58, 59, 113, 117; insulin resistance caused by, 56, 63, 64, 65, 68, 69, 70, 77; metabolic syndrome risk, 116, 125, 26; obesity as defense against, 113; toxicity of, 129, 31,
134, 35; type 2 diabetes caused by, 66, 181. See also insulin; insulin resistance hyperosmolar non-ketotic syndrome, 16, 124 hypertension (high blood pressure), 106, 107, 114, 15, 147 hypertriglyceridemia, 107, 109, 11 hypoglycemia: biguanide drugs and, 144; complications from, 123, 24; DPP-4 inhibitors and, 145; elevated glucose levels to avoid, 124; insulinomas and, 59; intensive insulin treatment and, 125; medication during fasting and, 200, 201 hypothalamic area, brain, 81
incretins, 144, 45, 148, 170 India, 3, 205 infections, 30, 31 insulin: carbohydrate-insulin hypothesis, 54, 55; as conventional diabetes treatment, 123; discovery of, 5, 7; dosage issues, 123, 24; energy storage-and-release role, 18, 49, 50, 53, 108, 9; failure to cure type 2 diabetes, 126, 29, 140, 148, 150, 206, 212; fasting insulin, 57, 58, 65, 169, 194; health costs from, 139; hypoglycemia from, 200; production by pancreas, 49; type 1 diabetes benefit, 124, 25; weight gain from, xiv, xv, 53, 54, 125, 127, 129.
See also hyperinsulinemia; insulin resistance insulin-dependent diabetes, 8 insulinoma, 53, 54, 59 insulin resistance: introduction, 20, 77; abdominal (visceral) fat role, 79, 90; beta cell dysfunction from, 78; caused by hyperinsulinemia, 56, 63, 64, 65, 68, 69, 70; de novo lipogenesis (DNL) and, 67, 70; emergence timeline prior to type 2 diabetes, 79; erectile dysfunction and, 31; fatty liver role, 80, 83; fatty muscle role, 86; fructose role, 100, 101, 182; high fasting insulin from, 65; intermittent fasting on, 194, 95; lock-and-key paradigm, 66, 68; obesity and, 57, 58; overflow phenomenon, xvi, xviii, 68, 71, 171; polycystic ovarian syndrome (PCOS) and, 32; as protective mechanism, 58, 59, 113, 117; Randle cycle and, 87; reversibility of, 59, 60.
See also hyperinsulinemia Intensive Dietary Management program, 201, 2, 216 INTERMAP study, 101 intermittent fasting.
See fasting, intermittent International Diabetes Federation, 11, 169 intrahepatic fat, 44.
See also fatty liver intramyocyte lipid accumulation, 85.
See also fatty muscle intra-organic fat, 44.
See also fat, abdominal iron supplements, 201
Japan, 10, 69, 176, 205 jejunocolic bypass surgery, 164, 65 jejunoileal bypass surgery, 165 Jenner, Edward, 62 Joslin, Elliott, 5, 6, 7, 8, 184, 190, 199 juvenile diabetes, 8, 18. See also type 1 diabetes
Kahn, Richard, 152 ketoacidosis, diabetic, 15, 16, 124, 146 Keys, Ancel, 94, 196 kidney disease (nephropathy), 23, 25 kidney infection, 30, 146 Kitava (island), 180
lactic acidosis, 144 Lana (case study), 209 Lantus, 139, 145 LCHF (low-carbohydrate, healthy-fat) diet, 40, 187, 88, 191, 198, 99, 215, 216 LDL (low-density lipoprotein), 108, 111 LEADER trial, 148 lean mass, 195, 197 leptin, 112, 13 lipodystrophy, 116, 17 lipoprotein lipase (LPL), 53, 111 Liraglutide, 148 liver, 108, 9. See also fatty liver lock-and-key paradigm, 66, 68 LookAHEAD (Action for Health in Diabetes) trial, 154, 55 low-carbohydrate, healthy-fat (LCHF) diet, 40, 187, 88, 191, 198, 99, 215, 216 low-carbohydrate diets, 4, 55, 174, 178, 79, 181, 182, 85 low-density lipoprotein (LDL), 108, 111 low-fat diets, 9, 40, 151, 152, 53, 175, 76. See also fat, dietary low glycemic-index diet, 178, 79 LPL (lipoprotein lipase), 53, 111 Ludwig, Jürgen, 81, 82 Lustig, Robert, 94, 103, 105 Lyon Diet Heart Study, 175
Macleod, John, 7 macronutrients, 50. See also carbohydrates; fat, dietary; protein macrovascular diseases, 26, 29; introduction, 22; atherosclerosis, 26, 27; heart disease, 27, 28; peripheral vascular disease (PVD), 28, 29; stroke, 28. See also cardiovascular (heart) disease madhumeha (honey urine), 3 magnesium supplements, 201 marbling, 86 medication: donations from pharmaceutical companies, 138, 39; failure of, xv, xviii, 126, 29, 148, 50, 212; fasting and, 200, 201; health costs from, 139; increase in types, 139; popularity despite lack of evidence, 138, 150; revenue from, 139 medication, specific types: overview, 149; acarbose, 147, 149; alpha-glucosidase inhibitors, 147; biguanide drugs, 144; dipeptidyl peptidase-4 (DPP-4) inhibitors, 144, 45, 149, 150, 200;
glucagon-like peptide 1 (GLP-1) analogs, 148, 149; insulin, 139, 140, 148, 150; metformin, 54, 127, 129, 143, 44, 149, 200, 201; pioglitazone (Actos), 142, 143; rosiglitazone (Avandia), 142, 43; sitagliptin, 145; sodium-glucose cotransporter 2 (SGL T 2), 145, 46, 149, 200; sulfonylureas (SUs), 54, 126, 128, 129, 141, 42, 148, 200; thiazolidinedione (TZD) drugs, 54, 128, 129, 142, 43, 148, 150 Mediterranean diet, 175, 76, 178, 79, 181 melatonin, 64 Mendonca, Suzanne, 196 Mering, Josef von, 5 metabolic syndrome (MetS): abdominal obesity and, 108, 113, 14; body’s protective mechanisms against, 116, 17; cause, 116, 117, 125, 26; definition, 106; discovery of, 107, 8; fatty liver and, 116; health risks from, 106, 115; high blood pressure (hypertension), 114, 15; high-density lipoproteins (HDL), 111, 12; hypertriglyceridemia, 109, 11; prevalence, 106, 108; progression, 115, 16; reversibility of, 117 metformin, 54, 127, 129, 143, 44, 149, 200, 201 micronutrients, 50 microvascular diseases, 23, 26; introduction, 22; nephropathy (kidney disease), 23, 25; neuropathy (nerve damage), 25, 26; retinopathy (eye disease), 23 Minkowski, Oskar, 5 Minnesota Starvation Experiment, 196 Montori, Victor, 150 Mosley, Michael, 41 muscles: fatty, 85, 86, 91; glycogen storage, 51, 85