Important Medical and Scientific Facts

1. Overweight, prediabetes and type 2 diabetes
Why is it important to avoid overweight and obesity? They cause insulin resistance which then lead to prediabetes, metabolic syndrome, atherosclerosis, macrovascular (cardiovascular) diseases and eventually develop into full blown type 2 diabetes and microvascular diseases. Actually, a lot of prediabetic people already have damage to cardiovascular system, hypertension, elevated LDL (low density cholesterol) and TG (triglycerides). Overweight is BMI (body mass index) >= 25, and obesity is BMI >=30. Prediabetes is defined as IFG (impaired fasting glucose, 100-125 mg/dl) and/or IGT (impaired glucose tolerance, 140-199 mg/dl in 2-H OGTT). Fasting blood sugar, OGTT (oral glucose tolerance test) with insulin level, triglycerides and lipid profile should be checked to find out prediabetes and/or metabolic syndrome.

An estimated 66 percent of U.S. adults are either overweight or obese. 41 million Americans have prediabetes, about 40% of all adults age 40-74 years, and the number is increasing and getting younger. 20 millions have diabetes (about 7% of population), of which 90% are type 2, developed from prediabetes usually within 10 years. 80% of individuals with type 2 diabetes are obese. Lifestyle modification resulting in a 5% to 7% weight loss lowered the incidence of type 2 diabetes by 58% after a 3.2-year follow-up period from previous study in Diabetes Prevention Program.

Drug intervention is less effective and costly with possible side effects. Currently, there are two drugs for obesity that are approved by the Food and Drug Administration for long-term use: sibutramine (Meridia, reduces appetite) and orlistat (Xenical, a lipase inhibitor, decreases dietary fat absorption by 30 percent). The latter is available over the counter.

2. Carbohydrates and Insulin
Excess intake of starchy and sugary food (white bread, white rice, potato, pasta, soft drinks, sweets, ice cream) leads to elevated blood glucose and increases insulin secretion. Insulin helps cells to metabolize glucose, to store excess glucose as glycogen and convert it into triglycerides. Too much insulin drastically drops the level of blood sugar and causes hunger 3-4 hours after meals. More eating produces more triglycerides, which are then stored in fat cells. Longer periods of elevated insulin and being overweight eventually cause insulin resistance and lead to metabolic syndrome and macrovascular (cardiovascular) disease. After several years, insulin resistance finally exhausts the beta cells in the pancreas and leads to overt type 2 diabetes.

The best way to increase insulin sensitivity is to lower your body weight and to exercise. Diet rich in fiber will slow and prolong the glucose absorption, and will prevent the blood sugar and insulin spike and hunger 3-4 hours after meals. But prediabetic people with elevated insulin due to insulin resistance are still going to be hungry, that is why snacks between meals are very important. Make sure total amount of calorie intake will be less than daily requirement (about 2,500 calories a day for men and 2,000 calories for women).

Small amount of fructose accelerates release of glucokinase, and then stimulates glycogen synthesis and increases hepatic glucose uptake in the presence of high glucose levels and thereby lower peripheral glycemia (In low glycemic state glusokinase reverses the direction and induces glycolysis). Fruits and vegetables, containing small amount of fructose, can have a positive effect for diabetic control. But too much high fructose sweeteners (sucrose and high-fructose corn syrup) leads to lipogenesis, triglycerides synthesis and insulin resistance. Fructose can only be metabolized or be stored as glycogen in liver. When liver's glycogen storage is full, fructose turns into fatty acids and triglycerides. Most of fruits and leafy vegetables have small amount of fructose. With high fiber content and slow absorption, their effect is beneficial. Fructose content in sucrose (table sugar) is 50% and high-fructose corn syrup is about 55%, and the latter is in most fruit drinks, soft drinks and as commercial food sweeteners. They certainly will lead to fat storage.

3. Metabolic Syndrome
Metabolic syndrome (syndrome X, obesity dyslipidemia syndrome, or best called insulin resistance syndrome) with insulin resistance and abdominal obesity leads to coronary artery disease and its sequelae, and plays a major role in developing Type 2 diabetes. The presence of any three of the following characteristics of the metabolic syndrome is sufficient to confirm the diagnosis. They are abdominal obesity (waist circumference: men>40in, women>35 in), low HDL cholesterol (men < 40 mg/dl, women < 50 mg/dl), elevated triglycerides (>=150mg/dl), high blood pressure (>=130/85 mm Hg) and elevated fasting glucose (100-125 mg/dl) or IGT (impaired glucose tolerance 2-H OGTT 140-199 mg/dl). It has been recognized that insulin resistance and its associated high risk for CVD precede the diagnosis of diabetes by 10-20 years.

There are several mechanisms to explain how obesity, especially visceral obesity, leads to insulin resistance and contributes to cardiovascular disease. Visceral adipocytes are far more metabolically active than subcutaneous adipocytes. Lipolysis (release of free fatty acids) from visceral fat is more pronounced than from subcutaneous fat, and visceral fat cells are less sensitive to suppression of lipolysis by insulin. Visceral fat has direct access to the portal circulation. Increased amounts of free fatty acids being released into the portal circulation may impair the metabolism and action of insulin and increase gluconeogenesis in the liver. Different mediators secreted by the adipocytes (esp. from visceral fat) have been implicated in the pathogenesis of insulin resistance associated with obesity. These mediators or chemical messengers, collectively known as "adipokines" include tumor necrosis factor (TNF)-a, adiponectin, interleukins, resistin, angiotensin II, C-reactive protein, free fatty acid, PAI-1 (plasminogen activator inhibitor--increase coagulability), and leptin. Adiponectin, reduced in obese people, appears to enhance insulin action, but it will increase appetite and slow down metabolism. Elevated leptin supposes to increase metabolism, suppress appetite and burn fat, but in the age of overeating, leptin resistance occurs and then the brain releases hunger signal instead. All the other adipokines are negatively affecting insulin sensitivity and cardiovascular system. Previous studies showed adiponectin reduces vascular inflammation, increases oxidation of free fatty acid and triglyceride, and reduces liver gluconeogenesis.

In metabolic syndrome, the cornerstone for management is to reduce the underlying cause, mainly obesity. For most patients, weight reduction and increased physical activity will reduce insulin resistance, hyperglycemia, hypertension, and dyslipidemia, and decrease the risk of cardiovascular disease. Specific therapies should also be targeted against the different components of the syndrome for each individual patient. Macrovascular (cardiovascular) disease is the major cause of morbidity and mortality, and these complications are established well before development of Type 2 diabetes. Early aggressive treatment aimed at reduction of visceral adiposity, glucose lowering, attention to blood pressure, dyslipidemia and prothrombotic state with insulin sensitizers (metformin and thiazolidinediones), statins, tissue-specific ACE inhibitors and aspirin are essential. Current recommendations for diabetic dyslipidemia advise that statin therapy should be routinely considered for all diabetics who are at risk for major vascular events, regardless of their baseline LDL.

4. Important fatty acids: Omega-3, 6, 9 fatty acids
Sunlight, chronic inflammation (as in metabolic syndrome), and many other exogenous and endogenous sources produce free radicals (chemical species that possess an unpaired electron in the outer shell of the molecule) in our body. Although some of the free radicals are necessary for life, they also trigger chains of chemical reactions and cause cell plasma membrane damage in multiple organs (including blood vessels) and block the cell's ability to utilize insulin effectively. This leads to the storage of body fat and weight gain. Antioxidants, such as vitamin A, vitamin C, vitamin E, alpha lipoic acid, coenzyme Q10, will block the free radicals, but will be depleted very quickly. Omega-3 essential fatty acids (polyunsaturated fats) can keep the cell membranes flexible, the receptors intact and sensitive to insulin. So diet rich in omega-3 fatty acids and fish oil supplements can have positive effect of burning sugar and fat, and avoiding storage of body fat. Omega-3 essential fatty acids can switch on key genes involved in burning fat and also involve in an energy metabolism and producing heat. In summary, omega-3 fatty acids have multiple energy producing pathways. So cold-water fish and supplemental fish oil and cod liver oil are greatly encouraged.

The omega-3 essential fatty acids in oily fish are called Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA), and they are considered much more valuable as these are the forms the body requires. In theory, humans are able to synthesize EPA and DHA from dietary ALA (alpha-linolenic acid), but in practice this process is inefficient. Scientists have therefore concluded that EPA and DHA should be obtained from diet. The richest sources of EPA and DHA are high-fat (10-15 per cent), cold-water fish like salmon, sardines, mackerel, anchovies, herring, trout and pilchards. EPA and DHA fatty acids make up 15-30 per cent of the oil content of these fish. Beside reducing insulin resistance, these two fatty acids play an important role as structural membrane lipids, and are pivotal in preventing heart disease, cancer, and many other diseases. The human brain is also highly dependent on DHA - low DHA levels have been linked to depression, schizophrenia, memory loss, and a higher risk of developing Alzheimer's.

Omega-6 fatty acids (Polyunsaturated fats) are essential to the proper development and functioning of the brain, reproductive systems, and metabolism, as well as helping maintain the health of skin and hair. Omega-6 fatty acids are 'essential fatty acids' that cannot be manufactured by the human body and must be ingested. Highest concentrations of this polyunsaturated fat are found in: soy, wheat, rice, hemp oils, grapeseed oil, and many nuts and seed. Excess intake of omega 6 can cause increased water retention, raised blood pressure and raised blood clotting. The typical American consumes far too much omega-6 fat in their diet while consuming very low levels of omega-3. The ideal ratio of omega-6 to omega-3 fats is 3:1 (suggestion ranging from 1:1 to 10:1). Today, though, our ratio averages from 20:1 to 50:1.

Omega-9 fatty acids (oleic acid, monounsaturated fatty acids) found in olive oil, acai fruit (berries), peanuts, and avocados. Omega-9 is not an 'essential fatty acid' meaning that it can be manufactured by the human body in limited quantities, unlike Omega-3 and Omega-6 fatty acids. It is used by the body to fight inflammation, decrease LDL, raise HDL, reduce atherosclerosis, balance blood sugar, and improve functioning of the immune system.

5. Exercise and Muscle Mass
Exercise increases metabolism and building muscle mass, and both will use more calories. Metabolism will also stay elevated for hours after exercise. Strenuous exercise will result in micro-trauma of the muscle, which will require energy to repair, and more calories will be burned. That is why exercise is such an efficient way to lose weight. Exercise and weight loss will increase insulin sensitivity, and can prevent or delay prediabetes from becoming diabetes. If you already have type 2 diabetes, losing weight and exercise can help you control your blood sugar levels and also may allow you to reduce the amount of diabetes medication you take. Exercise may be especially helpful in reducing the size of fat cells around the waistline. Diet alone showed no such change even with the similar weight loss. That’s important, because fat specifically in the abdomen has been linked to the risk of heart disease and diabetes. Usually exercise 30-45 minutes a day 5 days a week will be sufficient.

Prolong and excessive dieting causes shortage of calories, our body's natural response is to conserve fat and break down muscle tissue for fuel. About 25% of weight loss due to dieting can be muscle loss (as much as 50% in the self-imposed famine), and one pound of muscle loss will reduce energy requirement by about 50 calories a day just doing nothing. Reduced muscle mass will decrease metabolism and slow down weight loss. You will have to reduce even more calorie intake or to increase exercise to lose more weight. Older people gain weight not because of age. They are relatively inactive and losing muscle mass, so metabolism slow down and gain weight. Usually sedentary adult loses about 7 pounds of muscle every decade.

Dieting reduces blood sugar and decreases insulin secretion. In overweight or obese people, depleted insulin will reduce amino acids uptake by the muscle and causes reduction of muscle mass. Omega-3 fatty acid can help by increase insulin sensitivity. Excessive glycogen storage depletion will also enhance muscle wasting, that is why snacking between meals is important. Just don't snack within 3 hours before going to bed.

At certain point, if you can't lose any more weight, please don't worry. It is possible to gain about one pound of muscle per week and lose about one pound of fat per week. When you're strength training you can get smaller and heavier at the same time. Muscle is a much denser tissue than fat. The fat takes up more space on your body. Just rely on the way you look and the way your clothes fit. The scale can be misleading. Exercise (and adequate sleep) also releases growth hormone, which promotes growth in children and also serves many other metabolic functions as well. It increases calcium retention and bone density, increases muscle mass, promotes lipolysis and reduces body fat, increases protein synthesis and stimulates the growth of all internal organs except the brain, and stimulates the immune system.

6. Other important hormones: Glucagon, Leptin, Ghrelin and Incretin
Glucagon is released from pancreas when the glucose level in the blood is low, causing the liver to convert stored glycogen into glucose and release it into the bloodstream. The action of glucagon is opposite to that of insulin, which instructs the body's cells to metabolize glucose, to store excess glucose as glycogen and convert it into triglycerides.

Leptin (produced by adipose tissue) concentration correlates with body fat content and is usually increased in obese subjects but stays rather constant. Elevated plasma leptin due to sudden weight gain will increase metabolism, burn fat and reduce appetite. Dieting and exercise will depress leptin even before weight loss begins. That is why it is so difficult to lose weight, because fasting or following a low calorie diet lowers leptin level, which will increase appetite and store fat. One of leptin's main effects may be to inhibit synthesis and release of the hypothalamic neuropeptide Y, which increases food intake, decreases thermogenesis, and increases levels of insulin and corticosteroid in the plasma, and causes weight gain. Leptin resistance does occur in obase people because the capacity for transporting leptin across the blood-brain barrier is diminished, and then the brain releases hunger signal even when serum leptin is elevated. Lack of sleep also depresses leptin and causes weight gain. Simply, sudden leptin elevation reduces weight, and prolong increase in leptin due to persistant overeating and leptin resistance will store fat. Diet rich in Omega-3 fatty acid and exercise will increase leptin (and insulin) sensitivity and help weight loss. A decent breakfast is a good way to keep the leptin level high and prevent overeating later.

Ghrelin, which is considered the counterpart of leptin, is a hormone produced by fundus of the human stomach. Ghrelin levels increase before meals and decrease after meals. Hunger and lack of sleep produce Ghrelin, which stimulates appetite and reduces leptin.

Incretins are a type of GI hormone that causes an increase in insulin secretion after eating, even before blood glucose elevation. They also reduce gastric emptying and may directly reduce food intake. They also inhibit glucagon release from pancreas. GLP-1 (glucagon-like peptide-1) and GIP (gastric inhibitory peptide) are the two main incretins. They are rapidly inactivated by the enzyme DPP-4 (dipeptidyl peptidase 4). GLP-1 (7-36) amide (The sequence of GLP-1 has insulinotropic effect) analog, exenatide, has been used to increase insulin secretion, but it must be administered by subcutaneous injection. DPP-4 inhibitors, like Januvia (sitagliptin), can be taken orally and prevent inactivation of GLP-1 and GIP thus causing lowering of blood sugar.