HIPERCHOLESTEROLEMIA

Hypercholesterolemia, or high cholesterol, occurs when there is too much cholesterol in the body. Cholesterol is a soft, waxy, fat-like substance that is a natural component of all the cells in the body. Your body makes all the cholesterol it needs. Added cholesterol, which comes from the foods you eat, may cause harm.

High cholesterol raises your risk for heart disease, heart attack, and stroke. When there is too much cholesterol circulating in the blood, it can create sticky deposits (called plaque) along the artery walls. Plaque can eventually narrow or block the flow of blood to the brain, heart, and other organs. Blood cells that get caught on the plaque form clots, which can break loose and completely block blood flow through an artery, causing heart attack or stroke.

The normal range for total blood cholesterol is between 140 to 200 mg per decilitre (mg/dL) of blood (usually just expressed as a number). However, the total number doesn't tell the whole story: There are two types of cholesterol, HDL (high density lipoproteins, or "good" cholesterol) and LDL (low density lipoproteins, or "bad" cholesterol). The amount of HDL relative to LDL is considered a more important indicator of heart disease risk. There is a third kind of fatty material called triglycerides found in the blood. They also play a role (generally as triglyceride levels rise, "good" HDL cholesterol falls). In fact, there is a subset of physicians who believe that trigylcerides are the only fats in the body that increase heart disease risk. When you have high cholesterol, it usually means you have high levels of LDL cholesterol, normal or low levels of HDL cholesterol, and normal or high levels of triglycerides.

While heredity may be a factor for some people, the main culprits are lack of exercise and diets high in saturated fat. High cholesterol can be prevented, sometimes with lifestyle changes (diet and exercise) alone. If these do not work, your doctor may recommend medications to lower your cholesterol levels.

Signs and Symptoms

In the early stages, there usually aren't any symptoms of high cholesterol. The only way to tell if your cholesterol is high is through a blood test.

Causes

In some cases, high cholesterol levels may be inherited, your liver may make too much cholesterol, or your body may not remove LDL from your blood efficiently. High cholesterol and elevated triglycerides can also be associated with other diseases, such as diabetes. But most often high cholesterol is caused by eating foods high in saturated fat and not getting enough exercise. High cholesterol is more common in people who are overweight or obese, a condition that affects almost half of U.S. adults.

Risk Factors

Some factors increase a person's risk of having high cholesterol. While some of these cannot be changed, many can be. The most important risk factors for high cholesterol are:

• Being overweight or obese
• Eating a diet high in saturated fat and trans fatty acids (found in processed and fried foods)
• Not getting enough exercise
• Family history of heart disease
• High blood pressure
• Smoking
• Diabetes

Diagnosis

Most people do not have any symptoms of high cholesterol. A blood test is the only way to check levels of cholesterol in your blood. If your levels are above 200 mg/dL, or your HDL is below 40, your doctor may do a fasting lipid profile, a test performed after you abstain from food for 12 hours.

Although cholesterol levels above 200 are generally considered high, what is considered safe for each person depends on whether you are at risk for, or have, heart disease.

Total cholesterol levels:

• Desirable: Below 200 mg/dL
• Borderline high: 200 to 239
• High: Above 240

LDL cholesterol levels:

• Optimal for people with heart disease or who are at high risk: Below 70 mg/dL
• Optimal for people at risk of heart disease: Below 100
• Optimal: 100 to 129
• Borderline high: 130 to 159
• High: 160 to 189

HDL cholesterol levels:

• Poor: Below 40 mg/dL
• Acceptable: 40 to 59
• Optimal: 60 or above

Triglyceride levels:

• Optimal: Below 150 mg/dL
• Borderline high: 150 to 199
• High: Above 200

Adults with normal total and HDL cholesterol levels should have their cholesterol checked every 5 years. If you have high cholesterol, you should be checked every 2 to 6 months. You should have liver function tests as well if you are on cholesterol-lowering medication.

Preventive Care

Most people can lower cholesterol levels by eating a well balanced diet, getting regular exercise, and losing excess weight.

Diet

A healthy diet can help you lose weight. Losing just 5 or 10 pounds may help lower your cholesterol. To eat a healthy diet:

• Cut down on saturated fats and trans fats. No more than 10% of your daily calories should come from saturated fat, and you should avoid trans fats completely. Based on data from 4 studies, it is estimated that a 2% increase in energy intake from trans fats increases the incidence of heart disease by 23%. Choose unsaturated fats, such as olive oil and canola oil, instead.
• Eat whole grains, whole wheat bread and pasta, oatmeal, oat bran, and brown rice.
• Eat more fruits and vegetables, which are high in fiber and can help lower cholesterol levels. Studies show that plant-based diets are associated with decreases in total cholesterol and LDL cholesterol of up to 15%.
• Limit cholesterol in your diet. The highest amounts are found in egg yolks, whole milk products, and organ meats.
• Eat fatty fish. The American Heart Association (AHA) recommends that people eat at least 2 servings of fatty fish (such as salmon or herring) each week.
• Eat phytosterols and stanols found in nuts, seeds, vegetable oils, and fortified food products, such as orange juice, yogurt, and salad dressing. Studies show that eating 2 to 3 grams of phytosterols daily reduces total cholesterol by up to 11% and LDL cholesterol by up to 15%.
• Increase your intake of high fiber foods, especially oats, barley, and legumes, as well as fruits, vegetables, and other whole grains.

The AHA has developed dietary guidelines that help lower fat and cholesterol intake and reduce the risk of heart disease. The AHA does not recommend very low-fat diets, because new research shows that people benefit from unsaturated ("good") fats, such as those found in olive oil, avocados, and nuts.

Many fad diets are popular, but they may not help you lose weight and keep it off. In some cases, they may not even be healthy. A healthy diet includes a variety of foods. If a diet bans an entire food group (such as carbohydrates), it is probably not healthy.

Experts recommend eating a balanced diet that emphasizes fruit and vegetables:

• Grains: 6 to 8 servings per day (half should be whole grains)
• Vegetables: 3 to 5 servings per day
• Fruits: 4 to 5 servings per day
• Fat-free or low-fat dairy: 2 to 3 servings per day
• Lean meat, poultry, seafood: 3 to 6 oz. per day (about the size of a deck of cards)
• Fats and oils: 2 to 3 tbsp. per day (use unsaturated fats such as olive oil or canola oil)
• Nuts, seeds, legumes: 3 to 5 servings per week
• Sweets, sugars: 5 or fewer servings per week (the fewer, the better)

In addition, the AHA also recommends eating 2 servings of fatty fish (such as salmon, herring, or lake trout) per week; restricting sodium (salt, including salt already added to food) to less than 2,400 mg per day; and limiting alcohol intake to 1 drink a day for women and 2 for men. However, moderate alcohol consumption may help lower triglyceride levels and increase HDL levels.

The TLC (therapeutic lifestyle changes) diet is recommended for people who have high cholesterol. With the TLC diet, less than 7% of your daily total calories should come from saturated fat, and only 25% to 35% of your daily calories should come from fat, overall. Sodium should be limited to 2,400 mg per day. If these steps do not lower your cholesterol, your doctor may suggest adding more soluble fiber to your diet, along with plant sterols (found in cholesterol-lowering margarines and salad dressings).

The Mediterranean style diet concentrates on whole grains, fresh fruits and vegetables, fish, olive oil, and moderate, daily wine consumption. This diet is not low fat. It is low in saturated fat but high in monounsaturated fat. This diet is naturally rich in fiber, antioxidants, and omega-3 fatty acids. It appears to be heart healthy: In a long-term study of 423 people who had a heart attack, those who followed a Mediterranean style diet had a 50 to 70% lower risk of recurrent heart disease compared with people who received no special dietary counseling.

Losing Weight

Being overweight increases the risk of high cholesterol and heart disease. Even a 5 to 10 pound weight loss can lower LDL twice as much as diet alone. Weight loss often results in lower triglyceride levels and increased HDL, too. To maintain a healthy diet, you should aim for a gradual, weekly weight loss of 1/2 to 1 pound.

Getting Exercise

Regular exercise reduces the risk of death from heart disease and helps lower LDL cholesterol levels, especially when combined with a healthy diet. Just 30 minutes of moderate exercise 5 times per week can help you lose weight or maintain a proper weight, reduce LDL and triglyceride levels, and increase levels of HDL. Studies show that every 10 minutes of added exercise per session is associated with a 1.4 mg/dL increase in HDL cholesterol. Exercise may also lower blood pressure. Talk with your doctor before starting a new exercise program.

Treatment Approach

Lowering your cholesterol level reduces your risk of heart disease and stroke. Studies show that for every 1% reduction in cholesterol levels there is a 2% reduction in the rate of heart disease. People who already have heart disease or are at higher risk benefit most from lowering their cholesterol.

Changes in lifestyle, improved diet and more exercise, are the most effective means of both preventing and, in less severe cases, treating high LDL cholesterol levels. In addition to recommending lifestyle changes, doctors often prescribe specific cholesterol-lowering medications.

Medications

If your LDL cholesterol remains high, after changing your diet and exercise habits, your doctor may prescribe medications to lower it. If your cholesterol is very high (more than 200 mg/dL), you may start drug therapy at the same time you improve your diet and exercise habits. Drugs commonly used to treat high cholesterol include:

Statins: These are usually the drugs of choice as they are easy to take and have few interactions with other drugs. Side effects can include myositis (inflammation of the muscles), joint pain, stomach upset, and liver damage. People who are pregnant or have liver disease should not take statins. Statins include:

• Lovastatin (Mevachor)
• Pravastatin (Pravachol)
• Rosuvastatin (Crestor)
• Simvastatin (Zocor)
• Atorvastatin (Lipitor)
• Fluvastatin (Lescor)

Niacin (nicotinic acid): In prescription form, niacin is sometimes used to lower LDL cholesterol. It can be more effective in raising HDL cholesterol than other medications. Side effects may include redness or flushing of the skin (which can be reduced by taking aspirin 30 minutes before the niacin), stomach upset (which usually subsides in a few weeks), headache, dizziness, blurred vision, and liver damage. Dietary supplements of niacin should not be used instead of prescription niacin, as it can cause side effects. Only take niacin for high cholesterol under a doctor's supervision.

Bile acid sequestrants: These are used to treat high levels of LDL. Common side effects include bloating, constipation, heartburn, and elevated triglycerides. People who have high levels of triglycerides (fats in the blood) should not take bile acid sequestrants. These drugs include:

• Cholestyramine (Prevalite, Questran)
• Colestipol (Colestid)
• Colesevelam (WelChol)

Cholesterol absorption inhibitors: The medication ezetimibe (Zetia) limits how much LDL cholesterol can be absorbed in the small intestine. Side effects include headaches, nausea, muscle weakness. Ezetimibe is combined with simvastatin in the drug Vytorin.

Fibric acid derivatives: These medicines are effective at lowering triglyceride levels, and moderately effective at lowering LDL. They are used to treat high triglycerides and low HDL in people who cannot take niacin. Side effects include myositis, stomach upset, sun sensitivity, gallstones, irregular heartbeat, and liver damage.

• Gemfibrozil (Lopid)
• Fenofibrate (Tricor, Lofibra)

If you do not respond to one class of drugs, you doctor may use a combination of drugs from 2 classes.

Nutrition and Dietary Supplements

In addition to eating a healthy diet, low in saturated fat, with plenty of whole grains, fruits, and vegetables, some specific foods and supplements may help lower cholesterol.

Fiber: Several studies show that soluble fiber (found in beans, oat bran, barley, apples, psyllium, flaxseed, and glucomannan) lowers LDL cholesterol and triglycerides. Fiber can also help you lose weight because it makes you feel full. Your doctor will encourage you to get more fiber in your diet. You may also take a fiber supplement. Men should get 30 to 38 g of fiber per day. Women should get 21 to 25 g per day.

Beta-glucan is a type of soluble fiber found in oat bran and other plants. It slightly reduces LDL cholesterol, which is why oat bran is touted as a cholesterol-lowering food.

Soy: Many studies have shown that eating soy protein (tofu, tempeh, and miso), rather than animal meat, helps lower blood cholesterol levels, especially when you eat a diet low in saturated fat. One study found that as little as 20 g of soy protein per day is effective in reducing total cholesterol, and that 40 to 50 g shows faster effects (in 3 weeks instead of 6). Another study found that soy can help reduce triglyceride levels. The AHA recommends that people with elevated total and LDL cholesterol add soy to their daily diet, and that soy is safe when consumed as part of your regular diet. But talk to your doctor before you take soy supplements. Soy isoflavones may have estrogen-like effects in the body, which might lead to an increased risk of breast and other cancers.

Omega-3 fatty acids, found in fish oil: There is good evidence that omega-3 fatty acids (namely EPA and DHA) found in fish oil can help prevent heart disease, lower blood pressure, and reduce the level of triglycerides in the blood. However, fish oil can also raise levels of both HDL and LDL slightly. When taken as a supplement, it can also act as a blood thinner, so people who already take blood-thinning medication should only take a fish oil supplement under their doctor's supervision. One preliminary study found that people with high cholesterol who took fish oil and red yeast rice lowered cholesterol levels about as much as people who took simvastatin (Zocor). The AHA recommends that people eat at least 2 servings of fatty fish (such as salmon) per week, and that fish is safe when consumed as part of your regular diet. If you have high cholesterol, talk to your doctor before taking a fish oil supplement.

Alpha-linolenic acid (ALA): ALA is another omega-3 fatty acid that may protect the heart. However, studies have shown conflicting results about its ability to lower LDL, and it does not appear to lower triglyceride levels.

Vitamin C (100 to 200 mg per day): Several studies suggest that eating a diet high in vitamin C can help lower cholesterol levels, but there is no evidence that taking extra vitamin C through a supplement will help.

Beta-sitosterol (800 mg to 1 g per day in divided doses about 30 minutes before meals 3 times daily): Beta-sitosterol is a plant sterol, a compound that can stop cholesterol from being absorbed by the intestines. Several well-designed scientific studies have shown that beta-sitosterol does lower "bad" LDL cholesterol levels in the body. Beta-sitosterol may lower the amount of vitamin E and beta-carotene absorbed by the body, so you may want to ask your doctor if you need to take extra vitamin E or carotene.

Policosanol (5 to 10 mg 2 times per day): Policosanol is a mix of waxy alcohols usually derived from sugar cane and yams. Several studies have indicated it may lower "bad" LDL cholesterol and maybe even raise "good" HDL cholesterol. One study found that policosanol was equivalent to fluvastatin (Lescol) and simvastatin (Zocor) in lowering cholesterol levels. It may also inhibit blood clots from forming. However, almost all of the studies have been conducted in Cuba or Latin America using a proprietary form of policosanol, so it is hard to evaluate the evidence. Policosanol may increase the risk of bleeding, and should not be taken by people who also take blood-thinning medication.

Coenzyme Q10 (CoQ10): Researchers believe that CoQ10 may boost levels of antioxidants. One study found that people who received daily CoQ10 supplements within 3 days of a heart attack were much less likely to experience subsequent heart attacks and chest pain. They were also less likely to die of the condition than those who did not receive the supplements. Still, more research is needed to say whether CoQ10 has any role in preventing or treating atherosclerosis. People who take statins may have low levels of CoQ10. If you take statins, you may want to ask your doctor about taking a CoQ10 supplement. CoQ10 can interfere with anticoagulant / antiplatelet drugs.

Polyphenols: Polyphenols are chemical substances found in plants that have antioxidant properties. Test tube, animal, and some population-based studies suggest that the flavonoids quercetin, resveratrol, and catechins (all found in high concentration in red wine, and in grape juice) may help reduce the risk of atherosclerosis by protecting against the damage caused by LDL cholesterol. However, more studies in humans are needed to confirm these findings.

Resveratrol: A study in mice found that resveratrol protected against age-related damage to vital organs, including the heart and liver, even when the mice ate a high-fat diet. Although this study is promising, more studies are needed to determine whether resveratrol would have the same effect in humans. No one is sure how much resveratrol is needed to see a benefit. In addition, resveratrol may have estrogen-like effects, and researchers don't yet know whether it would pose the same risks as estrogen supplements. Resveratrol can potentially interact with a number of medications, including medications that are used to slow blood clotting, such as warfarin (Coumadin) and aspirin. If you take any prescription medications, check with your doctor before adding resveratrol to your regimen.

Herbs

The use of herbs is a time honored approach to strengthening the body and treating disease. However, herbs can trigger side effects and can interact with other herbs, supplements, or medications. For these reasons, you should take herbs with care and under the supervision of a health care provider.

Hawthorn (Crataegus monogyna, 900 to 1,800 mg per day in 2 to 3 divided doses): Hawthorn contains the polyphenols rutin and quercetin, and was traditionally used to treat cardiovascular diseases. Animal and laboratory studies show that hawthorn has antioxidant properties that may help lower high cholesterol and high blood pressure. Talk to your doctor before taking hawthorn, as it can interact with other drugs taken for heart disease and high blood pressure.

Garlic (Allium sativum, 900 mg per day of garlic powder, standardized to 0.6% allicin): Previous clinical trials have shown that fresh garlic and garlic supplements may lower cholesterol levels, prevent blood clots, and destroy plaque. However, more recent studies show no effect on cholesterol. Garlic can increase the risk of bleeding and should not be taken if you are also taking blood-thinning medication. Garlic may interact with Isoniazidand medications used to treat HIV/AIDS. Speak with your doctor.

Olive leaf extract (Olea europaea, 1000 mg per day): One study found that people with mild high blood pressure (hypertension) lowered cholesterol and blood pressure by taking olive leaf extract, compared to those who took placebo. More research is needed to confirm these findings.

Red yeast or red yeast rice (Monascus purpureus, 1,200 mg 2 times per day with meals): Several studies indicate that a proprietary form of red yeast (Cholestin) can lower cholesterol levels, and that the herb acts like prescription statin drugs (See "Medications" section). For that reason, you should not take red yeast without a doctor's supervision, especially if you already take statins to lower cholesterol.

Psyllium (Plantago psyllium, 10 to 30 g per day in divided doses taken 30 to 60 minutes after meals): Taking psyllium, a type of fiber, helps lower cholesterol levels, as well as blood sugar levels. If you take medicine for diabetes, talk to your doctor before taking psyllium.

Guggul (Commiphora mukul, 75 to 100 mg per day divided into 3 doses): Guggul is used in Ayurvedic medicine to treat high cholesterol levels. Scientific studies have found mixed results, guggul appears to work in Indian populations, but not in people who eat high-fat Western diets. Guggul may have estrogen-like properties. Take caution if you have a history of estrogen-sensitive cancers or if you're taking medications. Guggul can also affect thyroid function and therefore interact with thyroid medications. Speak with your doctor.

Other Considerations

Pregnancy

Cholesterol-lowering medications should be avoided during pregnancy.

Prognosis and Complications

Several complications may occur if high cholesterol is left untreated. These include:

• Heart disease. High cholesterol levels more than double the risk of heart attack. Lowering cholesterol by 1% reduces the risk of coronary artery disease by 2%.
• Stroke. Low levels of HDL ("good") cholesterol have been associated with an increased risk of stroke.
• Insulin resistance. 88% of people with low HDL and 84% with high triglycerides also have insulin resistance (which leads to high blood sugar levels). Many people with insulin resistance go on to develop diabetes.

Maintaining a proper weight, eating a diet low in saturated fat, and exercising can lower cholesterol levels and improve long-term prognosis.

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DIABETES MELLITUS

What is diabetes?

Diabetes mellitus is a group of metabolic diseases characterized by high blood sugar(glucose) levels that result from defects in insulin secretion, or its action, or both. Diabetes mellitus, commonly referred to as diabetes (as it will be in this article) was first identified as a disease associated with "sweet urine," and excessive muscle loss in the ancient world. Elevated levels of blood glucose (hyperglycemia) lead to spillage of glucose into the urine, hence the term sweet urine.

Normally, blood glucose levels are tightly controlled by insulin, a hormone produced by the pancreas. Insulin lowers the blood glucose level. When the blood glucose elevates (for example, after eating food), insulin is released from the pancreas to normalize the glucose level by promoting the uptake of glucose into body cells. In patients with diabetes, the absence of insufficient production of or lack of response to insulin causes hyperglycemia. Diabetes is a chronic medical condition, meaning that although it can be controlled, it lasts a lifetime.

6 early signs and symptoms of diabetes

1. The early symptoms of untreated diabetes are related to elevated blood sugar levels, and loss of glucose in the urine. High amounts of glucose in the urine can cause increased urine output and lead to dehydration. Dehydration causes increased thirst and water consumption.
2. The inability of insulin to perform normally has effects on protein, fat and carbohydrate metabolism. Insulin is an anabolic hormone, that is, one that encourages storage of fat and protein.
3. A relative or absolute insulin deficiency eventually leads to weight loss despite an increase in appetite.
4. Some untreated diabetes patients also complain of fatigue, nausea and vomiting.
5. Patients with diabetes are prone to developing infections of the bladder, skin, and vaginal areas.
6. Fluctuations in blood glucose levels can lead to blurred vision. Extremely elevated glucose levels can lead to lethargy and coma.

How do I know if I have diabetes?

Many people are unaware that they have diabetes, especially in its early stages when symptoms may not be present. There is no definite way to know if you have diabetes without undergoing blood tests to determine your blood glucose levels (see section on Diagnosis of diabetes). See your doctor if you have symptoms of diabetes or if you are concerned about your diabetes risk.

What causes diabetes?

Glucose is a simple sugar found in food. Glucose is an essential nutrient that provides energy for the proper functioning of the body cells. Carbohydrates are broken down in the small intestine and the glucose in digested food is then absorbed by the intestinal cells into the bloodstream, and is carried by the bloodstream to all the cells in the body where it is utilized. However, glucose cannot enter the cells alone and needs insulin to aid in its transport into the cells. Without insulin, the cells become starved of glucose energy despite the presence of abundant glucose in the bloodstream. In certain types of diabetes, the cells' inability to utilize glucose gives rise to the ironic situation of "starvation in the midst of plenty". The abundant, unutilized glucose is wastefully excreted in the urine.Insufficient production of insulin (either absolutely or relative to the body's needs), production of defective insulin (which is uncommon), or the inability of cells to use insulin properly and efficiently leads to hyperglycemia and diabetes. This latter condition affects mostly the cells of muscle and fat tissues, and results in a condition known as insulin resistance. This is the primary problem in type 2 diabetes. The absolute lack of insulin, usually secondary to a destructive process affecting the insulin-producing beta cells in the pancreas, is the main disorder in type 1 diabetes. In type 2 diabetes, there also is a steady decline of beta cells that adds to the process of elevated blood sugars. Essentially, if someone is resistant to insulin, the body can, to some degree, increase production of insulin and overcome the level of resistance. After time, if production decreases and insulin cannot be released as vigorously, hyperglycemia develops.

Insulin is a hormone that is produced by specialized cells (beta cells) of the pancreas. (The pancreas is a deep-seated organ in the abdomen located behind the stomach.) In addition to helping glucose enter the cells, insulin is also important in tightly regulating the level of glucose in the blood. After a meal, the blood glucose level rises. In response to the increased glucose level, the pancreas normally releases more insulin into the bloodstream to help glucose enter the cells and lower blood glucose levels after a meal. When the blood glucose levels are lowered, the insulin release from the pancreas is turned down. It is important to note that even in the fasting state there is a low steady release of insulin than fluctuates a bit and helps to maintain a steady blood sugar level during fasting. In normal individuals, such a regulatory system helps to keep blood glucose levels in a tightly controlled range. As outlined above, in patients with diabetes, the insulin is either absent, relatively insufficient for the body's needs, or not used properly by the body. All of these factors cause elevated levels of blood glucose (hyperglycemia).

What are the different types of diabetes?

There are two major types of diabetes, called type 1 and type 2. Type 1 diabetes was also formerly called insulin dependent diabetes mellitus (IDDM), or juvenile-onset diabetes mellitus. In type 1 diabetes, the pancreas undergoes an autoimmune attack by the body itself, and is rendered incapable of making insulin. Abnormal antibodies have been found in the majority of patients with type 1 diabetes. Antibodies are proteins in the blood that are part of the body's immune system. The patient with type 1 diabetes must rely on insulin medication for survival.

Type 1 diabetes

In autoimmune diseases, such as type 1 diabetes, the immune system mistakenly manufactures antibodies and inflammatory cells that are directed against and cause damage to patients' own body tissues. In persons with type 1 diabetes, the beta cells of the pancreas, which are responsible for insulin production, are attacked by the misdirected immune system. It is believed that the tendency to develop abnormal antibodies in type 1 diabetes is, in part, genetically inherited, though the details are not fully understood.

Exposure to certain viral infections (mumps and Coxsackie viruses) or other environmental toxins may serve to trigger abnormal antibody responses that cause damage to the pancreas cells where insulin is made. Some of the antibodies seen in type 1 diabetes include anti-islet cell antibodies, anti-insulin antibodies and anti-glutamic decarboxylase antibodies. These antibodies can be detected in the majority of patients, and may help determine which individuals are at risk for developing type 1 diabetes.

At present, the American Diabetes Association does not recommend general screening of the population for type 1 diabetes, though screening of high risk individuals, such as those with a first degree relative (sibling or parent) with type 1 diabetes should be encouraged. Type 1 diabetes tends to occur in young, lean individuals, usually before 30 years of age; however, older patients do present with this form of diabetes on occasion. This subgroup is referred to as latent autoimmune diabetes in adults (LADA). LADA is a slow, progressive form of type 1 diabetes. Of all the people with diabetes, only approximately 10% have type 1 diabetes and the remaining 90% have type 2 diabetes.

Type 2 diabetes

Type 2 diabetes was also previously referred to as non-insulin dependent diabetes mellitus (NIDDM), or adult-onset diabetes mellitus (AODM). In type 2 diabetes, patients can still produce insulin, but do so relatively inadequately for their body's needs, particularly in the face of insulin resistance as discussed above. In many cases this actually means the pancreas produces larger than normal quantities of insulin. A major feature of type 2 diabetes is a lack of sensitivity to insulin by the cells of the body (particularly fat and muscle cells).

In addition to the problems with an increase in insulin resistance, the release of insulin by the pancreas may also be defective and suboptimal. In fact, there is a known steady decline in beta cell production of insulin in type 2 diabetes that contributes to worsening glucose control. (This is a major factor for many patients with type 2 diabetes who ultimately require insulin therapy.) Finally, the liver in these patients continues to produce glucose through a process called gluconeogenesis despite elevated glucose levels. The control of gluconeogenesis becomes compromised.

While it is said that type 2 diabetes occurs mostly in individuals over 30 years old and the incidence increases with age, an alarming number of patients with type 2 diabetes are barely in their teen years. Most of these cases are a direct result of poor eating habits, higher body weight, and lack of exercise.

While there is a strong genetic component to developing this form of diabetes, there are other risk factors - the most significant of which is obesity. There is a direct relationship between the degree of obesity and the risk of developing type 2 diabetes, and this holds true in children as well as adults. It is estimated that the chance to develop diabetes doubles for every 20% increase over desirable body weight.

Regarding age, data shows that for each decade after 40 years of age regardless of weight there is an increase in incidence of diabetes. The prevalence of diabetes in persons 65 years of age and older is around 26%. Type 2 diabetes is also more common in certain ethnic groups. Compared with a 7% prevalence in non-Hispanic Caucasians, the prevalence in Asian Americans is estimated to be 9%, in Hispanics 13%, in blacks around 13%, and in certain Native American communities 20% to 50%. Finally, diabetes occurs much more frequently in women with a prior history of diabetes that develops during pregnancy (gestational diabetes).

What are the other types of diabetes?

Gestational diabetes

Diabetes can occur temporarily during pregnancy, and reports suggest that it occurs in 2% to 10% of all pregnancies. Significant hormonal changes during pregnancy can lead to blood sugar elevation in genetically predisposed individuals. Blood sugar elevation during pregnancy is called gestational diabetes. Gestational diabetes usually resolves once the baby is born. However, 35% to 60% of women with gestational diabetes will eventually develop type 2 diabetes over the next 10 to 20 years, especially in those who require insulin during pregnancy and those who remain overweight after their delivery. Women with gestational diabetes are usually asked to undergo an oral glucose tolerance test about six weeks after giving birth to determine if their diabetes has persisted beyond the pregnancy, or if any evidence (such as impaired glucose tolerance) is present that may be a clue to a risk for developing diabetes.

Secondary diabetes

"Secondary" diabetes refers to elevated blood sugar levels from another medical condition. Secondary diabetes may develop when the pancreatic tissue responsible for the production of insulin is destroyed by disease, such as chronic pancreatitis(inflammation of the pancreas by toxins like excessive alcohol), trauma, or surgical removal of the pancreas.

Hormonal disturbances

Diabetes can also result from other hormonal disturbances, such as excessive growth hormone production (acromegaly) and Cushing's syndrome. In acromegaly, a pituitary gland tumor at the base of the brain causes excessive production of growth hormone, leading to hyperglycemia. In Cushing's syndrome, the adrenal glands produce an excess of cortisol, which promotes blood sugar elevation.

Medications

Certain medications may worsen diabetes control, or "unmask" latent diabetes. This is seen most commonly when steroid medications (such as prednisone) are taken and also with medications used in the treatment of HIV infection (AIDS).

How is diabetes diagnosed?

The fasting blood glucose (sugar) test is the preferred way to diagnose diabetes. It is easy to perform and convenient. After the person has fasted overnight (at least 8 hours), a single sample of blood is drawn and sent to the laboratory for analysis. This can also be done accurately in a doctor's office using a glucose meter.

• Normal fasting plasma glucose levels are less than 100 milligrams per deciliter (mg/dl).
• Fasting plasma glucose levels of more than 126 mg/dl on two or more tests on different days indicate diabetes.
• A random blood glucose test can also be used to diagnose diabetes. A blood glucose level of 200 mg/dl or higher indicates diabetes.

When fasting blood glucose stays above 100mg/dl, but in the range of 100-126mg/dl, this is known as impaired fasting glucose (IFG). While patients with IFG or prediabetes do not have the diagnosis of diabetes, this condition carries with it its own risks and concerns, and is addressed elsewhere.

The oral glucose tolerance test

Though not routinely used any longer, the oral glucose tolerance test (OGTT) is a gold standard for making the diagnosis of type 2 diabetes. It is still commonly used for diagnosing gestational diabetes and in conditions of pre-diabetes, such as polycystic ovary syndrome. With an oral glucose tolerance test, the person fasts overnight (at least eight but not more than 16 hours). Then first, the fasting plasma glucose is tested. After this test, the person receives an oral dose (75 grams) of glucose. There are several methods employed by obstetricians to do this test, but the one described here is standard. Usually, the glucose is in a sweet-tasting liquid that the person drinks. Blood samples are taken at specific intervals to measure the blood glucose.

For the test to give reliable results:

• The person must be in good health (not have any other illnesses, not even a cold).
• The person should be normally active (not lying down, for example, as an inpatient in a hospital), and
• The person should not be taking medicines that could affect the blood glucose.
• The morning of the test, the person should not smoke or drink coffee.

The classic oral glucose tolerance test measures blood glucose levels five times over a period of three hours. Some physicians simply get a baseline blood sample followed by a sample two hours after drinking the glucose solution. In a person without diabetes, the glucose levels rise and then fall quickly. In someone with diabetes, glucose levels rise higher than normal and fail to come back down as fast.

People with glucose levels between normal and diabetic have impaired glucose tolerance (IGT) or insulin resistance. People with impaired glucose tolerance do not have diabetes, but are at high risk for progressing to diabetes. Each year, 1% to 5% of people whose test results show impaired glucose tolerance actually eventually develop diabetes. Weight loss and exercise may help people with impaired glucose tolerance return their glucose levels to normal. In addition, some physicians advocate the use of medications, such as metformin (Glucophage), to help prevent/delay the onset of overt diabetes.

Research has shown that impaired glucose tolerance itself may be a risk factor for the development of heart disease. In the medical community, most physicians now understand that impaired glucose tolerance is not simply a precursor of diabetes, but is its own clinical disease entity that requires treatment and monitoring.

Evaluating the results of the oral glucose tolerance test

Glucose tolerance tests may lead to one of the following diagnoses:

• Normal response: A person is said to have a normal response when the 2-hour glucose level is less than 140 mg/dl, and all values between 0 and 2 hours are less than 200 mg/dl.
• Impaired glucose tolerance (prediabetes): A person is said to have impaired glucose tolerance when the fasting plasma glucose is less than 126 mg/dl and the 2-hour glucose level is between 140 and 199 mg/dl.
• Diabetes: A person has diabetes when two diagnostic tests done on different days show that the blood glucose level is high.
• Gestational diabetes: A pregnant woman has gestational diabetes when she has any two of the following:, a fasting plasma glucose of 92 mg/dl or more, a 1-hour glucose level of 180 mg/dl or more, or a 2-hour glucose level of 153 mg/dl, or more.

Why is blood sugar checked at home?

There are some interesting developments in blood glucose monitoring including continuous glucose sensors. The new continuous glucose sensor systems involve an implantable cannula placed just under the skin in the abdomen or in the arm. This cannula allows for frequent sampling of blood glucose levels. Attached to this is a transmitter that sends the data to a pager-like device. This device has a visual screen that allows the wearer to see, not only the current glucose reading, but also the graphic trends. In some devices, the rate of change of blood sugar is also shown. There are alarms for low and high sugar levels. Certain models will alarm if the rate of change indicates the wearer is at risk for dropping or rising blood glucose too rapidly. One version is specifically designed to interface with their insulin pumps. In most cases the patient still must manually approve any insulin dose (the pump cannot blindly respond to the glucose information it receives, it can only give a calculated suggestion as to whether the wearer should give insulin, and if so, how much). 

However, in 2013 the US FDA approved the first artificial pancreas type device, meaning an implanted sensor and pump combination that stops insulin delivery when glucose levels reach a certain low point. All of these devices need to be correlated to fingersticks measurements for a few hours before they can function independently. The devices can then provide readings for 3 to 5 days.Home blood sugar (glucose) testing is an important part of controlling blood sugar. One important goal of diabetes treatment is to keep the blood glucose levels near the normal range of 70 to 120 mg/dl before meals and under 140 mg/dl at two hours after eating. Blood glucose levels are usually tested before and after meals, and at bedtime. The blood sugar level is typically determined by pricking a fingertip with a lancing device and applying the blood to a glucose meter, which reads the value. There are many meters on the market, for example, Accu-Check Advantage, One Touch Ultra, Sure Step and Freestyle. Each meter has its own advantages and disadvantages (some use less blood, some have a larger digital readout, some take a shorter time to give you results, etc). The test results are then used to help patients make adjustments in medications, diets, and physical activities.

Diabetes experts feel that these blood glucose monitoring devices give patients a significant amount of independence to manage their disease process; and they are a great tool for education as well. It is also important to remember that these devices can be used intermittently with fingerstick measurements. For example, a well-controlled patient with diabetes can rely on fingerstick glucose checks a few times a day and do well. If they become ill, if they decide to embark on a new exercise regimen, if they change their diet and so on, they can use the sensor to supplement their fingerstick regimen, providing more information on how they are responding to new lifestyle changes or stressors. This kind of system takes us one step closer to closing the loop, and to the development of an artificial pancreas that senses insulin requirements based on glucose levels and the body's needs and releases insulin accordingly - the ultimate goal.

Hemoglobin A1c (HBA1c)

To explain what hemoglobin A1c is, think in simple terms. Sugar sticks, and when it's around for a long time, it's harder to get it off. In the body, sugar sticks too, particularly to proteins. The red blood cells that circulate in the body live for about three months before they die off. When sugar sticks to these hemoglobin proteins in these cells, it is known as glycosylated hemoglobin or hemoglobin A1c (HBA1c). Measurement of HBA1c gives us an idea of how much sugar is present in the bloodstream for the preceding three months. In most labs, the normal range is 4%-5.9 %. In poorly controlled diabetes, its 8.0% or above, and in well controlled patients it's less than 7.0% (optimal is <6.5%). The benefits of measuring A1c is that is gives a more reasonable and stable view of what's happening over the course of time (three months), and the value does not vary as much as finger stick blood sugar measurements. There is a direct correlation between A1c levels and average blood sugar levels as follows.

While there are no guidelines to use A1c as a screening tool, it gives a physician a good idea that someone is diabetic if the value is elevated. Right now, it is used as a standard tool to determine blood sugar control in patients known to have diabetes.

HBA1c(%)	Mean blood sugar (mg/dl)
6	135
7	170
8	205
9	240
10	275
11	310
12	345

The American Diabetes Association currently recommends an A1c goal of less than 7.0% with A1C goal for selected individuals of as close to normal as possible (<6%) without significant hypoglycemia. Other Groups such as the American Association of Clinical Endocrinologists feel that an A1c of <6.5% should be the goal.

Of interest, studies have shown that there is about a 35% decrease in relative risk for microvascular disease for every 1% reduction in A1c. The closer to normal the A1c, the lower the absolute risk for microvascular complications.

It should be mentioned here that there are a number of conditions in which an A1c value may not be accurate. For example, with significant anemia, the red blood cell count is low, and thus the A1c is altered. This may also be the case in sickle cell disease and other hemoglobinopathies.

What are the acute complications of diabetes?

1. Severely elevated blood sugar levels due to an actual lack of insulin or a relative deficiency of insulin.
2. Abnormally low blood sugar levels due to too much insulin or other glucose-lowering medications.

Acute complications of type 2 diabetes

In patients with type 2 diabetes, stress, infection, and medications (such as corticosteroids) can also lead to severely elevated blood sugar levels. Accompanied by dehydration, severe blood sugar elevation in patients with type 2 diabetes can lead to an increase in blood osmolality (hyperosmolar state). This condition can worsen and lead to coma (hyperosmolar coma). A hyperosmolar coma usually occurs in elderly patients with type 2 diabetes. Like diabetic ketoacidosis, a hyperosmolar coma is a medical emergency. Immediate treatment with intravenous fluid and insulin is important in reversing the hyperosmolar state. Unlike patients with type 1 diabetes, patients with type 2 diabetes do not generally develop ketoacidosis solely on the basis of their diabetes. Since in general, type 2 diabetes occurs in an older population, concomitant medical conditions are more likely to be present, and these patients may actually be sicker overall. The complication and death rates from hyperosmolar coma is thus higher than in diabetic ketoacidosis.

Hypoglycemia means abnormally low blood sugar (glucose). In patients with diabetes, the most common cause of low blood sugar is excessive use of insulin or other glucose-lowering medications, to lower the blood sugar level in diabetic patients in the presence of a delayed or absent meal. When low blood sugar levels occur because of too much insulin, it is called an insulin reaction. Sometimes, low blood sugar can be the result of an insufficient caloric intake or sudden excessive physical exertion.

Blood glucose is essential for the proper functioning of brain cells. Therefore, low blood sugar can lead to central nervous system symptoms such as:

• dizziness,
• confusion,
• weakness, and
• tremors.

The actual level of blood sugar at which these symptoms occur varies with each person, but usually it occurs when blood sugars are less than 50 mg/dl. Untreated, severely low blood sugar levels can lead to coma,seizures, and, in the worst case scenario, irreversible brain death. 

The treatment of low blood sugar consists of administering a quickly absorbed glucose source. These include glucose containing drinks, such as orange juice, soft drinks (not sugar-free), or glucose tablets in doses of 15-20 grams at a time (for example, the equivalent of half a glass of juice). Even cake frosting applied inside the cheeks can work in a pinch if patient cooperation is difficult. If the individual becomes unconscious, glucagon can be given by intramuscular injection.

Glucagon is a hormone that causes the release of glucose from the liver (for example, it promotes gluconeogenesis). Glucagon can be lifesaving and every patient with diabetes who has a history of hypoglycemia (particularly those on insulin) should have a glucagon kit. Families and friends of those with diabetes need to be taught how to administer glucagon, since obviously the patients will not be able to do it themselves in an emergency situation. Another lifesaving device that should be mentioned is very simple; a medic-alert bracelet should be worn by all patients with diabetes.

Acute complications of type 1 diabetes

Insulin is vital to patients with type 1 diabetes - they cannot live without a source of exogenous insulin. Without insulin, patients with type 1 diabetes develop severely elevated blood sugar levels. This leads to increased urine glucose, which in turn leads to excessive loss of fluid and electrolytes in the urine. Lack of insulin also causes the inability to store fat and protein along with breakdown of existing fat and protein stores. This dysregulation, results in the process of ketosis and the release of ketones into the blood. Ketones turn the blood acidic, a condition called diabetic ketoacidosis (DKA). Symptoms of diabetic ketoacidosis include nausea, vomiting, and abdominal pain. Without prompt medical treatment, patients with diabetic ketoacidosis can rapidly go into shock, coma, and even death may result.

Diabetic ketoacidosis can be caused by infections, stress, or trauma, all of which may increase insulin requirements. In addition, missing doses of insulin is also an obvious risk factor for developing diabetic ketoacidosis. Urgent treatment of diabetic ketoacidosis involves the intravenous administration of fluid, electrolytes, and insulin, usually in a hospital intensive care unit. Dehydration can be very severe, and it is not unusual to need to replace 6-7 liters of fluid when a person presents in diabetic ketoacidosis. Antibiotics are given for infections. With treatment, abnormal blood sugar levels, ketone production, acidosis, and dehydration can be reversed rapidly, and patients can recover remarkably well.

What are the chronic complications of diabetes?

These diabetes complications are related to blood vessel diseases and are generally classified into small vessel disease, such as those involving the eyes, kidneys and nerves (microvascular disease), and large vessel disease involving the heart and blood vessels (macrovascular disease). Diabetes accelerates hardening of the arteries(atherosclerosis) of the larger blood vessels, leading to coronary heart disease(angina or heart attack), strokes, and pain in the lower extremities because of lack of blood supply (claudication).

Eye Complications

The major eye complication of diabetes is called diabetic retinopathy. Diabetic retinopathy occurs in patients who have had diabetes for at least five years. Diseased small blood vessels in the back of the eye cause the leakage of protein and blood in the retina. Disease in these blood vessels also causes the formation of small aneurysms (microaneurysms), and new but brittle blood vessels (neovascularization). Spontaneous bleeding from the new and brittle blood vessels can lead to retinal scarring and retinal detachment, thus impairing vision.

To treat diabetic retinopathy, a laser is used to destroy and prevent the recurrence of the development of these small aneurysms and brittle blood vessels. Approximately 50% of patients with diabetes will develop some degree of diabetic retinopathy after 10 years of diabetes, and 80% of diabetics have retinopathy after 15 years of the disease. Poor control of blood sugar and blood pressure further aggravates eye disease in diabetes.

Cataracts and glaucoma are also more common among diabetics. It is also important to note that since the lens of the eye lets water through, if blood sugar concentrations vary a lot, the lens of the eye will shrink and swell with fluid accordingly. As a result, blurry vision is very common in poorly controlled diabetes. Patients are usually discouraged from getting a new eyeglass prescription until their blood sugar is controlled. This allows for a more accurate assessment of what kind of glasses prescription is required.

Kidney damage

Kidney damage from diabetes is called diabetic nephropathy. The onset of kidney disease and its progression is extremely variable. Initially, diseased small blood vessels in the kidneys cause the leakage of protein in the urine. Later on, the kidneys lose their ability to cleanse and filter blood. The accumulation of toxic waste products in the blood leads to the need for dialysis. Dialysis involves using a machine that serves the function of the kidney by filtering and cleaning the blood. In patients who do not want to undergo chronic dialysis, kidney transplantation can be considered.

The progression of nephropathy in patients can be significantly slowed by controlling high blood pressure, and by aggressively treating high blood sugar levels. Angiotensin converting enzyme inhibitors (ACE inhibitors) or angiotensin receptor blockers (ARBs) used in treating high blood pressure may also benefit kidney disease in patients with diabetes.

Nerve damage

Nerve damage from diabetes is called diabetic neuropathy and is also caused by disease of small blood vessels. In essence, the blood flow to the nerves is limited, leaving the nerves without blood flow, and they get damaged or die as a result (a term known as ischemia). Symptoms of diabetic nerve damage include numbness, burning, and aching of the feet and lower extremities. When the nerve disease causes a complete loss of sensation in the feet, patients may not be aware of injuries to the feet, and fail to properly protect them. Shoes or other protection should be worn as much as possible. Seemingly minor skin injuries should be attended to promptly to avoid serious infections. Because of poor blood circulation, diabetic foot injuries may not heal. Sometimes, minor foot injuries can lead to serious infection, ulcers, and even gangrene, necessitating surgical amputation of toes, feet, and other infected parts.

Diabetic nerve damage can affect the nerves that are important for penile erection, causing erectile dysfunction (ED, impotence). Erectile dysfunction can also be caused by poor blood flow to the penis from diabetic blood vessel disease.

Diabetic neuropathy can also affect nerves to the stomach and intestines, causing nausea, weight loss, diarrhea, and other symptoms of gastroparesis (delayed emptying of food contents from the stomach into the intestines, due to ineffective contraction of the stomach muscles).

The pain of diabetic nerve damage may respond to traditional treatments with certain medications such as gabapentin (Neurontin), phenytoin (Dilantin), and carbamazepine (Tegretol) that are traditionally used in the treatment of seizure disorders. Amitriptyline (Elavil, Endep)and desipramine (Norpraminine) are medications that are traditionally used for depression. While many of these medications are not indicated specifically for the treatment of diabetes related nerve pain, they are used by physicians commonly.

The pain of diabetic nerve damage may also improve with better blood sugar control, though unfortunately blood glucose control and the course of neuropathy do not always go hand in hand. Newer medications for nerve pain include Pregabalin (Lyrica) and duloxetine (Cymbalta).

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