> AT ITS VERY core, type 2 diabetes can be understood as a disease caused by too much insulin, which our bodies secrete when we eat too much sugar. LOCATION: 159
> Type 2 diabetes is simply an overflow phenomenon that occurs when there is too much glucose in the entire body. LOCATION: 172
> WHAT HAPPENS WHEN excessive glucose piles up in the body over ten or twenty years? Every cell in the body starts to rot, which is precisely why type 2 diabetes, unlike virtually any other disease, affects every single organ. Your eyes rot, and you go blind. Your kidneys rot, and you need dialysis. Your heart rots, and you get heart attacks and heart failure. Your brain rots, and you get Alzheimer’s disease. Your liver rots, and you get fatty liver disease and cirrhosis. Your legs rot, and you get diabetic foot ulcers. Your nerves rot, and you get diabetic neuropathy. No part of your body is spared. LOCATION: 213
> You should maintain a moderate, not high, intake of protein. When it is digested, dietary protein, such as meat, breaks down into amino acids. Adequate protein is required for good health, but excess amino acids cannot be stored in the body and so the liver converts them into glucose. Therefore, eating too much protein adds sugar to the body. So you should avoid highly processed, concentrated protein sources such as protein shakes, protein bars, and protein powders. LOCATION: 232
> EXERCISE—BOTH RESISTANCE AND aerobic training—can have a beneficial effect on type 2 diabetes, but it is far less powerful at reversing the disease than dietary interventions. And fasting is the simplest and surest method to force your body to burn sugar. LOCATION: 243
> China, in particular, is a diabetes catastrophe. In 2013, an estimated 11.6 percent of Chinese adults had type 2 diabetes, eclipsing even the long-time champion, the U.S., at 11.3 percent.18 Since 2007, 22 million Chinese—a number close to the population of Australia—have been newly diagnosed with diabetes. This number is even more shocking when you consider that only 1 percent of Chinese had type 2 diabetes in 1980. In a single generation, the diabetes rate has risen by a horrifying 1160 percent. LOCATION: 388
> In the U.S., 14.3 percent of adults have type 2 diabetes and 38 percent of the population has prediabetes, totaling 52.3 percent. LOCATION: 393
> When blood glucose levels rise above the kidney’s ability to reabsorb the glucose (the renal threshold), it spills over into the urine, causing frequent, excessive urination and severe thirst. LOCATION: 434
> The amount of glucose attached to the hemoglobin can be measured with a simple blood test called the hemoglobin A1C. The A1C thus reflects the body’s average level of blood glucose over three months. LOCATION: 455
> Type 1 diabetes is an autoimmune disease, meaning that the body’s own immune system damages the cells that secrete insulin. LOCATION: 494
> There is a strong genetic predisposition to type 1 diabetes, but what eventually triggers the autoimmune destruction is uncertain. LOCATION: 497
> DIABETES IS THE leading cause of blindness in the United States. LOCATION: 545
> In type 1 diabetes, most patients develop some degree of retinopathy within twenty years. In type 2 diabetes, retinopathy may actually develop up to seven years before the diabetes itself is diagnosed. LOCATION: 555
> Diabetic kidney disease (nephropathy) is the leading cause of end stage renal disease (ESRD) in the United States, LOCATION: 561
> DIABETIC NERVE DAMAGE (neuropathy) affects approximately 60–70 percent of patients with diabetes. LOCATION: 574
> Significant nerve damage can lead to the complete destruction of the joint—a condition called Charcot foot—and may progress to the point where patients are unable to walk, and may even require amputation. LOCATION: 589
> Another nerve disorder affecting the large muscle groups is called diabetic amyotrophy, which is characterized by severe pain and muscle weakness, particularly in the thighs. LOCATION: 591
> No current treatment reverses diabetic nerve damage. Drugs may help the symptoms of the disease but do not change its natural history. Ultimately, it can only be prevented. LOCATION: 597
> Diabetes greatly increases the risk of developing atherosclerosis. LOCATION: 602
> Atherosclerosis is popularly but incorrectly imagined as cholesterol slowly clogging the arteries, much as sludge might build up in a pipe. In actuality, it results from injury to the artery, although the exact cause of the injury is unknown. LOCATION: 603
> HEART ATTACKS, KNOWN medically as myocardial infarctions, are the most well-recognized and feared complication of diabetes. They are caused by atherosclerosis of the blood vessels supplying the heart. The sudden blockage of these arteries starves the heart of LOCATION: 614
> Sixty-eight percent of diabetics aged sixty-five or older will die of heart disease, and a further 16 percent will die of stroke. LOCATION: 619
> A STROKE IS caused by atherosclerosis of the large blood vessels supplying the brain. A sudden disruption of the normal blood flow starves the brain of oxygen and a portion of the brain may die. LOCATION: 626
> Diabetes is a strong independent risk factor in stroke, meaning that, on its own, diabetes increases a person’s risk of having a stroke by as much as 150–400 percent. LOCATION: 629
> PERIPHERAL VASCULAR DISEASE (PVD) is caused by atherosclerosis of the large blood vessels supplying the legs. LOCATION: 635
> Skin with a poor blood supply is more likely to be damaged and takes longer to heal. In diabetics, minor cuts or injuries to the feet may become non-healing foot ulcers. In severe cases, these areas where the skin has broken down, revealing underlying tissue, can progress to gangrene. LOCATION: 639
> Diabetes, along with smoking, is the strongest risk factor for PVD. LOCATION: 643
> The links between Alzheimer’s disease and diabetes have grown so strong that many researchers have suggested Alzheimer’s disease can be called type 3 diabetes. LOCATION: 653
> NON-ALCOHOLIC FATTY liver disease (NAFLD) is defined as the storage and accumulation of excess fat in the form of triglycerides exceeding 5 percent of the total weight of the liver. LOCATION: 661
> Current estimates suggest that NAFLD affects 30 percent and NASH 5 percent of the U.S. population; both are important causes of liver cirrhosis (irreversible scarring of the liver). LOCATION: 664
> DIABETICS ARE MORE prone to all types of infections, which are caused by foreign organisms invading and multiplying in the body. Not only are they more susceptible to many types of bacterial and fungal infections than nondiabetics, the effects also tend to be more serious. LOCATION: 670
> Acanthosis nigricans is a gray-black, velvety thickening of the skin, particularly around the neck and in body folds, caused by high insulin levels. Diabetic dermopathy, also called shin spots, are often found on the lower extremities as dark, finely scaled lesions. Skin tags are soft protrusions of skin often found on the eyelids, neck, and armpits. Over 25 percent of patients with skin tags have diabetes. LOCATION: 685
> Nail problems are also common in diabetic patients, particularly fungal infections. The nails may become yellowy-brown, thicken, and separate from the nail bed (onycholysis). LOCATION: 689
> COMUNITY-BASED POPULATION studies of males aged 39–70 years found that the prevalence of impotence ranges between 10 and 50 percent. Diabetes is a key risk factor, increasing the risk of erectile dysfunction more than threefold and afflicting patients at a younger age than usual. LOCATION: 691
> PCOS is caused by elevated insulin resistance26 and increases the risk of developing type 2 diabetes three-to fivefold in young women. LOCATION: 701
> Diabetes and obesity are truly one and the same disease. LOCATION: 742
> Today, we understand clearly that obesity is the main underlying issue behind type 2 diabetes. But the problem isn’t simply obesity. Rather, it is abdominal obesity. LOCATION: 804
> body mass index is not the best indicator of type 2 diabetes risk. The waist circumference, a measure of body fat distribution around the trunk, is a far superior predictor of type 2 diabetes. LOCATION: 814
> Visceral fat accumulates inside and around the intra-abdominal organs such as the liver, kidneys, and intestines, and can be detected by an increased waist circumference. This pattern of obesity, where most of the fat is carried around the abdomen, is also known as central obesity, or central adiposity. In contrast, subcutaneous fat is the fat deposited directly under the skin. LOCATION: 821
> Independent of total weight, central obesity is highly correlated to metabolic abnormalities,14 increased cardiac risk,15 and progression to type 2 diabetes.16 Reducing visceral fat also successfully reduces the risk of progression of type 2 diabetes. LOCATION: 835
> Subcutaneous fat, on the other hand, shows little correlation to type 2 diabetes or heart disease. LOCATION: 839
> The waist-to-height ratio is a simple measure of central adiposity, calculated by comparing waist circumference to height. This ratio is far more predictive of years of life lost than body mass index.19 Optimally, your waist circumference should be less than half your height. For example, an average man standing 5 foot 10 inches (70 inches) should strive to maintain a waist size of 35 inches or less. As central obesity increases, risk of metabolic disease skyrockets. LOCATION: 842
> Fat within the liver, called intrahepatic fat, plays a crucial role in the development of insulin resistance.23 Central obesity tracks very closely with intrahepatic fat content.24 Fat within the pancreas also plays a leading role in type 2 diabetes, LOCATION: 854
> The truth is that the body can adjust its basal metabolic rate (BMR)—the energy required to keep the heart pumping, lungs breathing, kidneys and liver detoxifying, brain thinking, body generating heat, and so on—up or down by 40 percent. LOCATION: 877
> Contrary to many popular beliefs, we do not continue eating simply because food is available. Calorie consumption is under tight hormonal regulation. LOCATION: 925
> Fat accumulation is truly not a problem of energy excess. It’s a problem of energy distribution. LOCATION: 927
> Obesity is a hormonal imbalance, not a caloric one. The hormonal problem in undesired weight gain is mainly excessive insulin. Thus, type 2 diabetes, too, is a disease about insulin imbalance rather than caloric imbalance. LOCATION: 933
> Excessive insulin drives fat accumulation and obesity. How? If our feeding periods predominate over our fasting periods, then the ensuing insulin dominance leads to fat accumulation. Too much insulin signals the liver to keep admitting glucose, resulting in more production of new fat via DNL. Normally, if periods of high insulin (feeding) alternate with periods of low insulin (fasting), weight remains stable. If high insulin persists, the body receives the constant signal to store food energy as body fat. LOCATION: 1002
> Obese but otherwise normal (nondiabetic) patients have substantially increased insulin resistance compared to lean patients. LOCATION: 1056
> a ninety-six-hour constant intravenous infusion of insulin into a group of healthy young people increased insulin resistance by 20 to 40 percent. LOCATION: 1149
> Our bodies naturally defend against resistance by secreting our hormones in short bursts. LOCATION: 1158
> For resistance to develop, two essential factors are required: high hormonal levels and constant stimulus. LOCATION: 1169
> Obesity drives itself. LOCATION: 1185
> If high insulin levels have already jammed the cell full of glucose, no more can enter even if insulin opens the gate. From the outside, we can only say that the cell is now resistant to insulin’s urging to move glucose inside. LOCATION: 1241
> Insulin resistance is predominantly a glucose overflow problem of the overstuffed, fatty liver. LOCATION: 1268
> Excess dietary fat bypasses the liver and can be stored anywhere in the body. Fat carried under the skin (subcutaneous fat) contributes to overall weight and body mass index but has minimal health consequences. It is cosmetically undesirable but seems to be otherwise metabolically innocuous. LOCATION: 1326
> Excess dietary carbohydrates and protein are stored first in the liver as glycogen. Once glycogen stores are full, DNL converts glucose to fat, which can then be exported out of the liver to the rest of the body, including to fat stores in and around the abdominal organs. When DNL exceeds the export capacity of the liver, fat accumulates in the liver, where it contributes to central obesity and has dangerous health consequences. Too much sugar and insulin, over too long a period of time, leads to fatty liver. LOCATION: 1328
> Fatty liver is a completely reversible process. LOCATION: 1411
> You either burn sugar or fat, but not both. LOCATION: 1460
> First, beta cell function has been proven to be fully reversible. LOCATION: 1487
> The more fat found in the pancreas, the less insulin it secretes. LOCATION: 1510
> By weight, starches are approximately 70 percent amylopectin and 30 percent amylose (both are types of glucose chains). Animals, including humans, chain glucose molecules together as glycogen instead of starch. LOCATION: 1598
> Before the year 1900, the average person consumed 15 to 20 grams of fructose per day. LOCATION: 1614
> FRUCTOSE IS EVEN more strongly linked to obesity and diabetes than glucose is. LOCATION: 1631
> fructose is particularly malevolent to human health compared to glucose due to the unique way the body metabolizes it. LOCATION: 1633
> When we eat large quantities of fructose, on the other hand, it heads straight to the liver, since no other cells can use or metabolize it. Consider what this means for an average person weighing 170 pounds. Sucrose provides equal amounts of glucose and fructose. Whereas all 170 pounds of the body metabolize the glucose, the 5-pound liver must valiantly metabolize the equivalent amount of fructose all on its own. LOCATION: 1639
> Fructose overfeeding can increase DNL fivefold,6 and replacing glucose with a calorically equal amount of fructose increases liver fat by a massive 38 percent within only eight days. LOCATION: 1649
> The way the body metabolizes ethanol (alcohol) is quite similar. Once ingested, tissues can only metabolize 20 percent of the alcohol, leaving 80 percent targeted straight to the liver.7 The liver metabolizes it to acetaldehyde, which stimulates de novo lipogenesis, so alcohol, like fructose, easily becomes liver fat.8 This explains the well-known effect of alcohol consumption in producing fatty liver disease. LOCATION: 1658
> Remarkably, it only takes one week of excess fructose to cause insulin resistance. It only takes eight weeks to allow prediabetes to establish a beachhead. LOCATION: 1673
> fructose has no alternative runoff pathway. The liver stores excess glucose safely and easily as glycogen, breaking it back down into glucose when the body needs access to energy. On the other hand, the body cannot store fructose directly. When the body has enough energy to meet its actual needs, the liver metabolizes fructose into fat through a process that cannot be easily reversed. LOCATION: 1714
> Eating dietary carbohydrates, not dietary saturated fat, increases saturated fat levels in the blood. Saturated fats in the blood, not the diet, are highly associated with heart disease. LOCATION: 1797
> The two main activators of DNL are insulin and excessive dietary fructose. LOCATION: 1806
> High dietary intake of carbohydrates—and to a lesser extent, protein—stimulates insulin secretion and provides the substrate for DNL. LOCATION: 1806
> higher insulin levels and fructose ingestion produce higher blood triglyceride levels. There’s just too much sugar. LOCATION: 1830
> High levels of LDL are pointedly not one of the criteria for developing metabolic syndrome. LOCATION: 1845
> The landmark Framingham studies established that low levels of HDL are strongly associated with heart disease22 and predicts heart disease much more powerfully than LDL. LOCATION: 1847
> What is clear, however, is that the lipid profile typical of the metabolic syndrome—high triglycerides and low HDL—results from the excess of VLDL,25 which ultimately stems from hyperinsulinemia, which ultimately stems from eating too much glucose and fructose. LOCATION: 1856
> The predominance of fat around the abdomen becomes noticeable as an increase in waist size, which can be described as a beer belly but more recently is being called a “wheat belly.” This abdominal, or visceral, fat is the most important predictor of metabolic syndrome. LOCATION: 1881
> Surgical removal of visceral fat reverses insulin resistance,27 whereas removal of subcutaneous fat has no such metabolic benefits. LOCATION: 1883
> Insulin increases blood pressure through multiple mechanisms.33 Insulin increases the cardiac output—the contractile force of the heart34—and the volume of blood in circulation by enhancing the kidney’s ability to reabsorb sodium (salt). In addition, insulin stimulates the secretion of anti-diuretic hormone, which helps the body to reabsorb water. LOCATION: 1902
> Obesity, insulin resistance, and beta cell dysfunction are all protective mechanisms. Obesity tries to prevent DNL from overwhelming the liver by safely storing the newly created fat in the adipocytes. LOCATION: 1928
> insulin resistance is the body’s attempt to prevent fat from amassing in the internal organs by preventing it from entering. LOCATION: 1936
> The final line of defense lies in shutting down pancreatic production of insulin. Blood glucose rapidly rises above the renal threshold and causes all the classic symptoms of diabetes. LOCATION: 1939
> In type 1 diabetes, blood insulin is low, so replacing insulin is logical. In type 2, blood insulin is high, so giving more insulin seems problematic. LOCATION: 2075
> WHILE TYPE 2 diabetes is associated with numerous complications, including nerve, kidney, and eye damage, the morbidity and mortality associated with cardiovascular diseases is the most important.21 Simply put, most diabetic patients die of cardiovascular disease. LOCATION: 2153
> Treating type 2 diabetes with insulin was not good; it was bad. Simply put, the higher the insulin dose, the higher the risk of dying. LOCATION: 2181
> Excessive insulin is toxic, particularly in a setting of type 2 diabetes, where baseline insulin is already very high. Giving more insulin will lower the blood glucose, but worsen the underlying hyperinsulinemia. Trading insulin toxicity for glucotoxicity is not beneficial. LOCATION: 2191
> DIABETES, AS WELL as obesity and prediabetes, increases the risk of many different types of cancer, including breast, colon, endometrial, kidney, and bladder cancers. LOCATION: 2194
> cancer cells are highly metabolically active and need large supplies of glucose to proliferate. LOCATION: 2211
> SULFONYLUREAS STIMULATE THE pancreas to produce more insulin, thereby effectively reducing blood sugars. LOCATION: 2258
> In 1999, the Federal Drug Administration (FDA) approved the first new diabetes drug class in more than a decade, the thiazolidinediones (TZDs). These drugs bind to receptors in the fat cells, making them more sensitive to insulin and thereby amplifying insulin’s effects. LOCATION: 2283
> Biguanides work by blocking gluconeogenesis and thereby preventing the liver from producing glucose. LOCATION: 2317
> IN 2006, the FDA approved a new class of medications called the dipeptidyl peptidase-4 (DPP-4) inhibitors. These drugs are designed to lower blood glucose by blocking the breakdown of incretins, which are hormones released in the stomach that increase insulin secretion in response to food. LOCATION: 2331
> THE NEWEST CLASS of medications, called sodium-glucose cotransporter 2 (SGLT2) inhibitors, block glucose reabsorption in the kidney, allowing glucose to escape in the urine, which replicates the protective mechanism used by the body during severe hyperglycemia. LOCATION: 2348
> GLUCAGON-LIKE PEPTIDE 1 (GLP-1) analogs are diabetic medications that mimic the effect of the incretin hormones. LOCATION: 2390
> insulin treatment, including medications that simulate only the blood glucose–lowering properties of insulin, carries no perceptible benefits and significant risks. Insulin is “significantly more harmful than other active treatments.” LOCATION: 2429
> Removing fat from the organs leads to rapid metabolic improvement. Removing excess fat from the pancreas resolves beta cell dysfunction. As insulin secretion returns to normal, blood glucose begins to drop. Removing the excess fat from the liver, like deflating that overinflated balloon, reverses insulin resistance. The dual defects of type 2 diabetes resolve. LOCATION: 2718
> High blood levels of trans-palmitoleic acid from full-fat dairy are associated with a 60 percent reduction in the incidence of type 2 diabetes. It also improves HDL triglyceride levels and lowers markers of inflammation, such as high-sensitivity C-reactive protein. LOCATION: 2800
> Egg yolks, once reviled as being high in cholesterol, have been vindicated. Studies now conclude that eating eggs, even daily, does not raise the risk of heart disease.15 In fact, consuming lots of eggs reduces the risk of diabetes by 42 percent. LOCATION: 2802
> FASTING, THE VOLUNTARY abstinence from food, has been known to cure diabetes for close to 100 years. LOCATION: 2985
> bariatrics is surgically enforced fasting. LOCATION: 2995
> Twenty-two days of alternate daily fasting also did not result in any decrease in basal metabolic rate. LOCATION: 3097
> Fasting lowers insulin maximally, so it is quite simply the quickest and most efficient method. Still, the very low–carbohydrate diet does remarkably well, giving you 71 percent of the benefits of the fasting without actual fasting. LOCATION: 3121
> Compared to the standard 55 percent carbohydrate diet, low-carbohydrate diets reduce insulin by roughly half, despite similar calorie intakes. Fasting reduces that by another 50 percent. LOCATION: 3124
> In my Intensive Dietary Management program, we often start with a thirty-six-hour fasting period three times per week for type 2 diabetes. During the eating periods, we prescribe a low-carbohydrate, high-fat diet. We provide strict medical supervision for patients, and frequent follow-up visits are essential. After they begin, we adjust the fasting schedule for each patient according to how they respond. LOCATION: 3172