FDA's Role in Regulating Food and Diet

FDA's Center for Food Safety and Applied Nutrition (CFSAN), in conjunction with the Agency's field staff, is responsible for promoting and protecting the public's health by ensuring that the nation's food supply is safe, sanitary, wholesome, and honestly labeled. The Center's primary responsibilities include:

• the safety of substances added to food, e.g., food additives (including ionizing radiation) and color additives
  
• the safety of foods and ingredients developed through biotechnology
  
• seafood Hazard Analysis and Critical Control Point (HACCP) regulations
  
• regulatory and research programs to address health risks associated with foodborne chemical, and biological contaminants
  
• regulations and activities dealing with the proper labeling of foods (e.g., ingredients, nutrition health claims) and cosmetics
  
• regulations and policy governing the safety of dietary supplements, infant formulas, and medical foods
  
• safe and properly labeled cosmetic ingredients and products
  
• food industry postmarket surveillance and compliance
  
• consumer education and industry outreach
  
• cooperative programs with state and local governments
  
• international food standard and safety harmonization efforts

Dietary Supplements

Congress defined the term "dietary supplement" in the Dietary Supplement Health and Education Act (DSHEA) of 1994. A dietary supplement is a product taken by mouth that contains a "dietary ingredient" intended to supplement the diet. The "dietary ingredients" in these products may include: vitamins, minerals, herbs or other botanicals, amino acids, and substances such as enzymes, organ tissues, glandulars, and metabolites. Dietary supplements can also be extracts or concentrates, and may be found in many forms such as tablets, capsules, softgels, gelcaps, liquids, or powders. They can also be in other forms, such as a bar, but if they are, information on their label must not represent the product as a conventional food or a sole item of a meal or diet. Whatever their form may be, DSHEA places dietary supplements in a special category under the general umbrella of "foods," not drugs, and requires that every supplement be labeled a dietary supplement.

In October 1994, the Dietary Supplement Health and Education Act (DSHEA) was signed into law by President Clinton. Before this time, dietary supplements were subject to the same regulatory requirements as were other foods. This new law, which amended the Federal Food, Drug, and Cosmetic Act, created a new regulatory framework for the safety and labeling of dietary supplements.

Under DSHEA, a firm is responsible for determining that the dietary supplements it manufactures or distributes are safe and that any representations or claims made about them are substantiated by adequate evidence to show that they are not false or misleading. This means that dietary supplements do not need approval from FDA before they are marketed. Except in the case of a new dietary ingredient, where pre-market review for safety data and other information is required by law, a firm does not have to provide FDA with the evidence it relies on to substantiate safety or effectiveness before or after it markets its products.

Also, manufacturers do not need to register themselves nor their dietary supplement products with FDA before producing or selling them. Currently, there are no FDA regulations that are specific to dietary supplements that establish a minimum standard of practice for manufacturing dietary supplements. However, FDA intends to issue regulations on good manufacturing practices that will focus on practices that ensure the identity, purity, quality, strength and composition of dietary supplements. At present, the manufacturer is responsible for establishing its own manufacturing practice guidelines to ensure that the dietary supplements it produces are safe and contain the ingredients listed on the label.

People with diabetes should be sure to consult a doctor or pharmacist before purchasing or taking any supplement. Many supplements contain active ingredients that have strong biological effects and their safety is not always assured in all users. Other supplements may interact with prescription and over-the-counter medicines. By taking these products, you may be placing yourself at risk.

Overweight, Obesity, and Weight-Loss

More than 60 percent of U.S. adults are either overweight or obese, according to the Centers for Disease Control and Prevention (CDC). While the number of overweight people has been slowly climbing since the 1980s, the number of obese adults has nearly doubled since then.

Excess weight and physical inactivity account for more than 300,000 premature deaths each year in the United States, second only to deaths related to smoking, says the CDC. People who are overweight or obese are more likely to develop heart disease, stroke, high blood pressure, diabetes, gallbladder disease and joint pain caused by excess uric acid (gout). Excess weight can also cause interrupted breathing during sleep (sleep apnea) and wearing away of the joints (osteoarthritis).

To address the public health epidemic of being overweight or obese, former Surgeon General David Satcher issued a "call to action" in December 2001. Satcher's report, The Surgeon General's Call to Action to Prevent and Decrease Overweight and Obesity, outlined strategies that communities can use in helping to address the problems. Those options included requiring physical education at all school grades, providing more healthy food options on school campuses, and providing safe and accessible recreational facilities for residents of all ages.

Using the food label to help with food choices

Under regulations from the Food and Drug Administration of the Department of Health and Human Services and the Food Safety and Inspection Service of the U.S. Department of Agriculture, the food label offers more complete, useful and accurate nutrition information than ever before.

With today's food labels, consumers get

• nutrition information about almost every food in the grocery store
  
• distinctive, easy-to-read formats that enable consumers to more quickly find the information they need to make healthful food choices
  
• information on the amount per serving of saturated fat, cholesterol, dietary fiber, and other nutrients of major health concern
  
• nutrient reference values, expressed as % Daily Values, that help consumers see how a food fits into an overall daily diet
  
• uniform definitions for terms that describe a food's nutrient content--such as "light," "low-fat," and "high-fiber"--to ensure that such terms mean the same for any product on which they appear
  
• claims about the relationship between a nutrient or food and a disease or health-related condition, such as calcium and osteoporosis, and fat and cancer. These are helpful for people who are concerned about eating foods that may help keep them healthier longer.
  
• standardized serving sizes that make nutritional comparisons of similar products easier
  
• declaration of total percentage of juice in juice drinks. This enables consumers to know exactly how much juice is in a product.

Begin with the Nutrition Facts panel, usually on the side or back of the package. The Nutrition Facts panel has two parts: The main or top section, which contains product-specific information (serving size, calories, and nutrient information) that varies with each food product; and the bottom part, which contains a footnote. This footnote is only on larger packages and provides general dietary information about important nutrients.

Several features of the Nutrition Panel help people with diabetes manage their diets. First of all, serving sizes now are more uniform among similar products and reflect the amounts people actually eat. The similarity makes it easier to compare the nutritional qualities of related foods. People who use the Exchange Lists should be aware that the serving size on the label may not be the same as that in the Exchange Lists. For example, the label serving size for orange juice is 8 fluid ounces (240 milliliters). In the exchange lists, the serving size is 4 ounces (one-half cup) or 120 mL. So, a person who drinks one cup of orange juice has used two fruit exchanges.

The label also gives grams of total carbohydrate, protein and fat, which can be used for carbohydrate counting. The values listed for total carbohydrates include all carbohydrates, including dietary fiber and sugars listed below it. Not singled out is complex carbohydrates, such as starches. The sugars include naturally present sugars, such as lactose in milk and fructose in fruits, and those added to the food, such as table sugar, corn syrup, and dextrose. The listing of grams of protein also is helpful for those restricting their protein intake, either to reduce their risk of kidney disease or to manage the kidney disease they have developed.

Elsewhere on the label, consumers may find claims about the food's nutritional benefits. These claims signal that the food contains desirable levels of certain nutrients. Some claims, such as "low fat," "no saturated fat," and "high fiber," describe nutrient levels. Some of these are particularly interesting to people with diabetes because they highlight foods containing nutrients at beneficial levels.

Other claims, called health claims, show a relationship between a nutrient or food and a disease or health condition. FDA has authorized a number of claims, which are based on significant scientific agreement. Three claims that relate to heart disease are of particular interest to people with diabetes:

• A diet low in saturated fat and cholesterol may help reduce the risk of coronary heart disease.
• A diet rich in fruits, vegetables and grain products that contain fiber, particularly soluble fiber, and are low in saturated fat and cholesterol may help reduce the risk of coronary heart disease.
• Soluble fiber from whole oats, as part of a diet low in saturated fat and cholesterol, may help reduce the risk of coronary heart disease.

Nutrient and health claims can be used only under certain circumstances, such as when the food contains appropriate levels of the stated nutrients.

The Food Guide Pyramid

The Food Guide Pyramid can help you put the Dietary Guidelines into action. The pyramid illustrates the research-based food guidance developed by the U.S. Department of Agriculture and supported by the Department of Health and Human Services. It is based on USDA's research on what foods Americans eat, what nutrients are in these foods, and how to make the best food choices to promote good health. It outlines what to eat each day, but it is not a rigid prescription. You can use it as a general guide in choosing a healthful diet that is right for you. The pyramid calls for eating a variety of foods to get the nutrients you need, and, at the same time, the right amount of calories to maintain a healthy weight.

The food guide pyramid is shown below:

Selecting Foods for a Healthy Meal Plan

By following the government's Dietary Guidelines for Americans, you can promote your health and reduce your risk for chronic diseases such as heart disease, certain types of cancer, diabetes, stroke, and osteoporosis. These diseases are leading causes of death and disability among Americans. Good diets can also reduce major risk factors for chronic disease-such as obesity, high blood pressure, and high blood cholesterol. Your food choices, your lifestyle, your environment, and your family history all affect your well-being. It is important for everyone to follow the 10 Dietary Guidelines listed below. If you are at higher risk of having a chronic disease, it is especially important.

The Dietary Guidelines for Americans include the following:

AIM FOR FITNESS . . .

• Aim for a healthy weight.
  
• Be physically active each day.

BUILD A HEALTHY BASE . . .

• Let the Pyramid guide your food choices.
  
• Choose a variety of grains daily, especially whole grains.
  
• Choose a variety of fruits and vegetables daily.
  
• Keep food safe to eat.

CHOOSE SENSIBLY . . .

• Choose a diet that is low in saturated fat and cholesterol and moderate in total fat.
  
• Choose beverages and foods to moderate your intake of sugars.
  
• Choose and prepare foods with less salt.
• If you drink alcoholic beverages, do so in moderation.
  

Some people with diabetes use the Exchange Lists for Meal Planning. This system, established by the American Dietetic and American Diabetes associations, separates foods into six categories based on their nutritional makeup. People following this plan choose a set number of servings from each category daily, depending on their nutritional needs.

Food and Meal Planning

Food and Meal Planning

Because food intake affects the body's need for insulin and insulin's ability to lower blood sugar, diet is the cornerstone of diabetes treatment. Today, diabetes experts no longer recommend a single meal plan for all people with diabetes. Instead, they recommend meal plans that are flexible and take into account a person's lifestyle and particular health needs. The American Diabetes Association recommends that people with diabetes consult a registered dietician to design a meal plan.

Food and Meal Planning

• Selecting Foods for a Healthy Meal Plan
• The Food Guide Pyramid

• 
  Using the food label to help with food choices

• Overweight, Obesity, and Weight-Loss
• Dietary Supplements

• 
  FDA's Role in Regulating Food and Diet

Complications of Diabetes

Complications of Diabetes

Over time, diabetes can lead to heart and blood vessel disease, blindness, kidney failure, and foot ulcers, among other conditions. FDA regulates many products to treat these conditions

Complications of Diabetes

Heart and Blood Vessel Disease

Heart disease is the leading cause of death for people with diabetes.

Three out of four diabetes-related deaths are caused by heart and blood vessel (cardiovascular) disease. People with diabetes are 2-4 times more likely to have heart disease than persons without diabetes. Even people with type 2 diabetes who do not have heart disease have an increased risk of having a heart attack. People with diabetes also tend to have other risk factors for heart disease including obesity, high blood pressure, and hardening of the arteries (atherosclerosis).

In recent years, FDA has approved drugs that lower blood pressure and reduce the risk of heart attacks and strokes. It has also approved lipid-altering drugs that target abnormalities of cholesterol and triglycerides.

Blindness

Adults with diabetes should have yearly eye exams to ensure the health of their eyes and to protect their vision.

Over time, high blood sugar levels can damage the blood vessels that feed the retina of the eye. In nonproliferative diabetic retinopathy (NPDR), an early stage of diabetic eye disease, the blood vessels may leak fluid. This may cause the retina to swell and vision to blur, a condition called diabetic macular edema. In advanced or proliferative diabetic retinopathy (PDR), abnormal new blood vessels grow on the surface of the retina. The abnormal blood vessels don't supply the retina with normal blood flow. In addition, they may eventually pull on the retina and cause it to detach.

Some cases of diabetic retinopathy can be treated with laser surgery. In this procedure, doctors aim a strong beam of light onto the patient's retina to shrink or seal leaking or abnormal vessels. Laser surgery can't restore vision already lost, so early detection is important. In some advanced cases of PDR, a surgeon may remove the vitreous portion of the eye and replace it with a clear solution (called a vitrectomy).

Kidney Failure

Over time, high blood sugar levels can damage the kidneys. Even when drugs and diet are able to control diabetes, the disease can lead to kidney disease (diabetic nephropathy) and kidney failure.

Healthy kidneys act like filters to clean the blood of waste products and extra fluid. Damaged kidneys do not clean the blood well. Instead, waste products and fluid build up in the blood.

People with kidney failure must either have dialysis treatment (to substitute for some of the filtering functions of the kidneys) or receive a kidney transplant.

FDA regulates dialysis equipment. The agency does not inspect dialysis clinics--that is the responsibility of each state health department--but FDA approves the equipment used in dialysis. Recently, the agency has begun requiring that hemodialyzer filters and tubes be tested and approved in realistic clinical situations. For example, in about eight out of 10 hemodialysis treatments, the equipment is reused to cut costs, although it was originally tested, labeled and approved for one-time use only. FDA is now requiring manufacturers to prove that filters and tubes are safe and effective when reused. FDA is also taking a closer look at water purifying equipment used in dialysis. Pure water is crucial to hemodialysis, since impurities can kill a patient. FDA has recently begun enforcing regulations that require the manufacturers of water purifiers to prove their devices are safe and effective.

Foot Ulcers

Adults with diabetes need to take special care of their feet.

People with diabetes are at risk for foot injuries due to numbness caused by nerve damage (diabetic neuropathy) and low blood flow to the legs and feet. The most serious injury is a foot ulcer. Diabetic foot ulcers are at very high risk of becoming infected, and sometimes they cannot be healed. Non-healing foot ulcers are a frequent cause of amputation in people with diabetes. Patients with foot ulcers may use wound dressings, skin substitutes, or other treatments to protect and heal their skin.

Wound dressings are medical devices that are used to protect ulcerated skin and assist in its healing. They can range from simple bandages that you can buy in the drug store to complex materials that contain antibacterial and antiviral substances.

Skin substitutes are products that help in closing the wounds of slow healing ulcers in patients with diabetes. They are made from human cells known as fibroblasts that are placed on a dissolvable mesh material. When the mesh material is placed on the ulcer, it is gradually absorbed and the human cells grow and replace the damaged tissue in the ulcer.

FDA has cleared one gel product (becaplermin) that is used as a treatment for diabetic foot ulcers. This product contains genetically engineered platelet-derived growth factor, one of the proteins the body produces to encourage new tissue growth. Clinical studies of the product indicated that the likelihood of complete ulcer closure, after up to 20 weeks of treatment, was greater when becaplermin is used.

What is insulin pumps?

Insulin Pumps

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If you have been diagnosed with diabetes, you may feel overwhelmed by all the new information you have learned and will continue to learn about managing your diabetes. You already know your main goal should be to get your blood glucose (sugar) levels under control in order to increase your chances of a complication-free life. Many people know this, but need to know how to achieve good diabetes management, while balancing the day-to-day demands of diabetes with other life demands.

An insulin pump can help you manage your diabetes. By using an insulin pump, you can match your insulin to your lifestyle, rather than getting an insulin injection and matching your life to how the insulin is working. When you work closely with your diabetes care team, insulin pumps can help you keep your blood glucose levels within your target ranges. People of all ages with type 1 diabetes use insulin pumps and people with type 2 diabetes have started to use them as well.

How do insulin pumps work?

Insulin pumps deliver rapid- or short-acting insulin 24 hours a day through a catheter placed under the skin. Your insulin doses are separated into:

• Basal rates
• bolus doses to cover carbohydrate in meals
  
• Correction or supplemental doses
  

Basal insulin is delivered continuously over 24 hours, and keeps your blood glucose levels in range between meals and overnight. Often, you program different amounts of insulin at different times of the day and night.

When you eat, you use buttons on the insulin pump to give additional insulin called a bolus. You take a bolus to cover the carbohydrate in each meal or snack. If you eat more than you planned, you can simply program a larger bolus of insulin to cover it.

You also take a bolus to treat high blood glucose levels. If you have high blood glucose levels before you eat, you give a correction or supplemental bolus of insulin to bring it back to your target range.

Knowing how an insulin pump works is one thing. But you may be wondering where you are supposed to put it. You can buy a pump case or it can be attached to a waistband, pocket, bra, garter belt, sock, or underwear. You can also tuck any excess tubing into the waistband of your underwear or pants.

When you sleep, you could try laying the pump next to you on the bed. You could even try wearing it on a waistband, armband, legband, or clip it to the blanket, sheet, pajamas, stuffed toy, or pillow with a belt clip.

Showering and bathing are other instances when you should know where to put your insulin pump. Although insulin pumps are water resistant, they should not be set directly in the water. Instead, you can disconnect it. All insulin pumps have a disconnect port for activities, such as swimming, bathing, or showering. Some pumps can be placed on the side of the tub, in a shower caddy, or in a soap tray. There are also special cases you can buy. You can hang these cases from your neck or from a shower curtain hook.

No matter what you may think, you can still have fun when you are using an insulin pump. When you exercise or play sports, you can wear a strong elastic waist band with a pump case. You can also wear it on an armband where it is visible. Women can tape the insulin pump to the front of their sports bra. Some coaches do not allow any devices to be worn because getting the pump knocked into you or falling on it can be painful. In this case, you may just need to take the insulin pump off.

When you disconnect your pump, you are stopping all delivery (basal and bolus) by the pump. Here are some important tips to remember when disconnecting your pump.

1. It is important for you to remember that if you stop your pump while it is in the middle of delivering any bolus -- it will NOT be resumed. You may need to program a new one.



2. Be sure to bolus to cover the basal rate you will miss. If your blood glucose level is under 150, you can wait an hour to bolus.



3. Do not go longer than one to two hours without any insulin.



4. Monitor your blood glucose every three to four hours.

Now that you know how the insulin pump works and how to wear it, take a look at some of the facts to see if this is right for you.

Advantages of Using an Insulin Pump

Some advantages of using an insulin pump instead of insulin injections are:

• Using an insulin pump means eliminating individual insulin injections



• Insulin pumps deliver insulin more accurately than injections



• Insulin pumps often improve A1C



• Using an insulin pump usually results in fewer large swings in your blood glucose levels



• Using an insulin pump makes diabetes management easier – if your glucose level is high or you feel like eating, figure out how much insulin you need and push the little button on the pump



• Insulin pumps allow you to be flexible about when and what you eat



• Using an insulin pump can improve your quality of life



• Using an insulin pump reduces severe low blood glucose episodes



• Using an insulin pump eliminates unpredictable effects of intermediate- or long-acting insulin



• Insulin pumps allow you to exercise without having to eat large amounts of carbohydrate

Although there are many good reasons as to why using an insulin pump can be an advantage, there are some disadvantages.

Disadvantages of Using an Insulin Pump

The disadvantages of using a pump are that it:

• Can cause weight gain
  

• Can cause diabeteic ketoacidosis (DKA) if your catheter comes out and you don’t get insulin for hours
  

• Can be expensive
  

• Can be bothersome since you are attached to the pump most of the time
  

• Can require a hospital stay or maybe a full day in the outpatient center to be trained
  

There are pluses and minuses to using a pump. Even though using an insulin pump has disadvantages, most pump users agree the advantages outweigh the disadvantages.

Getting Started

Once you have talked with your diabetes care team and have become comfortable with all of the options on your insulin pump, you and your team will need to do the following in order to get you started.

1. Determine how much insulin to use in the insulin pump by averaging the total units of insulin you use per day for several days. (You may start with about 20% less if you are switching to rapid-acting insulin.)



2. Divide the total dosage into 40-50% for basal and 50-60% for bolus insulin.



3. Divide the basal portion by 24 to determine a beginning hourly basal rate.



4. Then, adjust the hourly basal rate up or down for patterns of highs and lows, such as more insulin for dawn phenomenon and less for daily activity.



5. Determine a beginning carbohydrate dose (insulin:carb ratio) using the 450 (or 500) rule. Divide by the total units of insulin/day to get the number of grams of carbohydrate covered by one unit of insulin. This dose may be raised or lowered based on your history and how much fast-acting insulin you took in the past.



6. Determine the dose of insulin to correct high blood glucose with the 1800 (or 1500) rule. Divide 1800 by the total units of insulin/day to see how much one unit of insulin lowers your blood glucose. This dose must be evaluated by your health care team. It is often too high for children or for people who have not had diabetes very long.

It may take several months to get comfortable with the pump. During those first months is the time to adopt some good habits. Here are some tips to help you adjust:

• Take your insulin at a specific time, such as five minutes before you eat, so you don't forget boluses.
  
• When traveling anywhere, bring extra supplies or at least an insulin pen, in case you are unable to use your pump for some reason.
  
• With an insulin pump, when you eat, what you eat, and how much you eat is up to you. You can eat more carbohydrate and still manage your blood glucose, but weight gain can happen. Talk to a dietitian about this when you start on the pump. It's a lot easier to not to gain weight, than it is to lose it after you have already gained it.
  
• When you take the insulin pump off or turn it off, figure out a system to remember to turn it back on. Listen to the alarms on the pump or set a timer!
  
• Make a habit of recording blood glucose checks, carbohydrate amounts, carbohydrate doses, correction doses, and exercise when you do them. It really helps to sit down and look over your blood glucose record at the end of every week (or even every day) to see if you have any problem areas. Reviewing your records is the key to improving blood glucose control.
  
• Your diabetes provider and insulin pump company have record forms, or you can make your own. Just be sure that you have enough room to record everything you need. Keeping daily records is best, but some people find keeping records for two weekdays and one weekend day gives enough information to see the patterns.

This is a lot of information. Fortunately, you don't need to be an expert on insulin pumps overnight. If you are uncertain about anything, you can go to your diabetes care team for help. Everyone learns at a different pace and it is okay if it takes you a while to get the hang of it.

Type II Diabetes -- Genetic Factors

Type II Diabetes -- Genetic Factors

Normally, genetic studies are conducted by a classical linkage analysis using an LOD (Logarithm of Odds) score. This type of pedigreed, generational study works well if the disease is an autosomal dominant, recessive disorder. A study of this kind focuses on a particular gene locus to see if it tracks or co-segregates with the disease.

The problem with diabetes is that, even if the exact same mutation caused it in everyone, it would look different from person to person and family to family, depending on environmental influences, the genetic background it's laid upon, and modifier genes. Its expression would be variable.Furthermore, studies have shown that diabetes is not simple; it's genetically complex, involving multiple genes, and multiple gene-environment interactions.

Since classical linkage analysis doesn't work very well when studying genes in a mixed population, geneticists are moving to sib-pair analysis, called IBD - Identity by Descent. Siblings share 50% of their genes. If a gene locus has no association with a disease, it would be predicted that the siblings would share the locus 50% of the time.

One new, and somewhat controversial, method of studying the genetic component of diabetes is an Admixture Linkage Analysis. In this method, researchers view the admixed population as an F1 cross. If a disease is linked to a chromosomal locus in a genetically distinct population, it will stay in linkage association for multiple generations, until it finally sorts out through recombination. Since it's been 15 generations or so since the Europeans came over and admixed with the Native American population, now is the perfect time to do this kind of linkage analysis. The idea is that since DNA is inherited as a block, a gene locus and a marker will stay in association longer, the closer they are on the chromosome - if they are far away, the marker will fall out and they will no longer be linked.

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Major Susceptibility Locus for Type II Diabetes

There have been several different regions of the human genome associated with susceptibility to Type II diabetes. One locus on the distal part of the long arm of chromosome 2 in the human genome has been well characterized to be linked with type II diabetes in humans. Information about this locus can be obtained at:

OMIMNIDDM

"Hanis et al. (1996) performed a genome-wide search that revealed a major susceptibility locus for noninsulin dependent diabetes mellitus (125853) on chromosome 2. The study was performed on 330 affected sibpairs from Mexican American families living close to the Rio Grande River in Texas. Marker D2S125, which is located in the distal part of the long arm of chromosome 2, showed significant evidence of linkage to NIDDM and appeared to be a major factor affecting the development of diabetes mellitus in Mexican Americans. Hanis et al. (1996) proposed that the locus be designated NIDDM1."

Hanis, C. L.; Boerwinkle, E.; Chakraborty, R.; Ellsworth, D. L.; Concannon, P.; Stirling, B.; Morrison, V. A.; Wapelhorst, B.; Spielman, R. S.; Gogolin-Ewens, K. J.; Shephard, J. M.; Williams, S. R.; Risch, N.; Hinds, D.; Iwasaki, N.; Ogata, M.; Omori, Y.; Petzold, C.; Rietzsch, H.; Schroder, H.-E.; Schulze, J.; Cox, N. J.; Menzel, S.; Boriraj, V. V.; Chen, X.; Lim, L. R.; Lindner, T.; Mereu, L. E.; Wang, Y.-Q.; Xiang, K.; Yamagata, K.; Yang, Y.; Bell, G. I.: A genome-wide search for human non-insulin-dependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2. Nature Genet. 13: 161-166, 1996.

Genecard for diabetes mellilitus 2

Rebhan, M., Chalifa-Caspi, V., Prilusky, J., Lancet, D.: GeneCards: encyclopedia for genes, proteins and diseases. Weizmann Institute of Science, Bioinformatics Unit and Genome Center (Rehovot, Israel), 1997. GeneCard for Diabetes mellilitus type 2 (NIDDM 1)

Information about animal models for diabetes can be obtained at:

OMIMNIDDM"Discussion of the polygenic or at least digenic inheritance of diabetes in mouse and rat models with pointers to related genetic studies in humans."

Transplantation in diabetes

Transplantation

In recent years, researchers have focused increasing attention on transplantation for people with type 1 diabetes. Current procedures include:

• Pancreas transplantation. Pancreas transplants have been performed since the late 1960s. Most are done in conjunction with or after a kidney transplant. Kidney failure is one of the most common complications of diabetes, and receiving a new pancreas when you receive a new kidney may actually improve kidney survival. Furthermore, after a successful pancreas transplant, many people with diabetes no longer need to use insulin. Unfortunately, pancreas transplants aren't always successful. Your body may reject the new organ days or even years after the transplant, which means you'll need to take immunosuppressive drugs the rest of your life. These drugs are costly and can have serious side effects, including a high risk of infection and organ injury. Because the side effects can be more dangerous to your health than your diabetes, you're usually not considered a candidate for transplantation unless your diabetes can't be controlled or you're experiencing serious complications. On the other hand, pancreas transplantation may be an option if you are age 45 or younger, have type 1 diabetes and need or have had a kidney transplant, or if insulin doesn't control your blood sugar.

• Islet cell transplantation. Your pancreas contains about 1 million islet cells, 75 percent to 80 percent of which produce insulin. The beta cells that produce insulin reside in the islets. Although still considered an experimental procedure, transplanting these cells may offer a less invasive, less expensive and less risky option than a pancreas transplant for people with diabetes. In islet cell transplantation, doctors infuse fresh pancreas cells into the liver of the person with diabetes. The cells spread throughout the liver and soon begin to produce insulin. The liver, not the pancreas, is the site of the transplant because it's easier to access the large portal vein in your liver than it is to access a vein in your pancreas. What's more, cells that grow in the liver secrete insulin much like cells in the pancreas do.

Medications

Medications

When diet, exercise and maintaining a healthy weight aren't enough, you may need the help of medication. Medications used to treat diabetes include insulin. Everyone with type 1 diabetes and some people with type 2 diabetes must take insulin every day to replace what their pancreas is unable to produce. Unfortunately, insulin can't be taken in pill form because enzymes in your stomach break it down so that it becomes ineffective. For that reason, many people inject themselves with insulin using a syringe or an insulin pen injector ? a device that looks like a pen, except the cartridge is filled with insulin. Others may use an insulin pump, which provides a continuous supply of insulin, eliminating the need for daily shots.

An insulin pump is a pumping device about the size of a deck of cards. You wear it outside your body. A small tube connects the reservoir of insulin to a catheter that's inserted under the skin of your abdomen. The pump dispenses the desired amount of insulin into your body and can be adjusted to infuse more or less insulin depending on meals, activity and glucose level. Insulin pumps aren't for everyone. But for some people they provide improved blood sugar control and a more flexible lifestyle.

The most widely used form of insulin is synthetic human insulin, which is chemically identical to human insulin but manufactured in a laboratory. Unfortunately, synthetic human insulin isn't perfect. One of its chief failings is that it doesn't mimic the way natural insulin is secreted. But newer types of insulin, known as insulin analogs, more closely resemble the way natural insulin acts in your body. Among these are lispro (Humalog), insulin aspart (NovoLog) and glargine (Lantus).

A number of drug options exist for treating type 2 diabetes, including:

• Sulfonylurea drugs. These medications stimulate your pancreas to produce and release more insulin. For them to be effective, your pancreas must produce some insulin on its own. Second-generation sulfonylureas such are prescribed most often. The most common side effect of sulfonylureas is low blood sugar, especially during the first four months of therapy. You're at much greater risk of low blood sugar if you have impaired liver or kidney function.

• Meglitinides. These medications, such as repaglinide have effects similar to sulfonylureas, but you're not as likely to develop low blood sugar. Meglitinides work quickly, and the results fade rapidly.

• Biguanides. Metformin is the only drug in this class available in the United States. It works by inhibiting the production and release of glucose from your liver, which means you need less insulin to transport blood sugar into your cells. One advantage of metformin is that is tends to cause less weight gain than do other diabetes medications. Possible side effects include a metallic taste in your mouth, loss of appetite, nausea or vomiting, abdominal bloating, or pain, gas and diarrhea. These effects usually decrease over time and are less likely to occur if you take the medication with food. A rare but serious side effect is lactic acidosis, which results when lactic acid builds up in your body. Symptoms include tiredness, weakness, muscle aches, dizziness and drowsiness. Lactic acidosis is especially likely to occur if you mix this medication with alcohol or have impaired kidney function.

• Alpha-glucosidase inhibitors. These drugs block the action of enzymes in your digestive tract that break down carbohydrates. That means sugar is absorbed into your bloodstream more slowly, which helps prevent the rapid rise in blood sugar that usually occurs right after a meal. Drugs in this class include acarbose (Precose) and miglitol . Although safe and effective, alpha-glucosidase inhibitors can cause abdominal bloating, gas and diarrhea. If taken in high doses, they may also cause reversible liver damage.

• Thiazolidinediones. These drugs make your body tissues more sensitive to insulin and keep your liver from overproducing glucose. Side effects of thiazolidinediones, such as rosiglitazone and pioglitazone hydrochloride , include swelling, weight gain and fatigue. A far more serious potential side effect is liver damage. The thiazolidinedione troglitzeone was taken off the market in March 2000 because it caused liver failure. If your doctor prescribes these drugs, it's important to have your liver checked every two months during the first year of therapy. Contact your doctor immediately if you experience any of the signs and symptoms of liver damage, such as nausea and vomiting, abdominal pain, loss of appetite, dark urine, or yellowing of your skin and the whites of your eyes (jaundice). These may not always be related to diabetes medications, but your doctor will need to investigate all possible causes.

• Drug combinations. By combining drugs from different classes, you may be able to control your blood sugar in several different ways. Each class of oral medication can be combined with drugs from any other class. Most doctors prescribe two drugs in combination, although sometimes three drugs may be prescribed. Newer medications, such as Glucovance, which contains both glyburide and metformin, combine different oral drugs in a single tablet.

How to moniter blood sugar and maintein it?

Monitoring blood sugar

If you've just received a diagnosis of diabetes, monitoring your blood sugar may seem like an overwhelming task. But once you learn to measure your blood sugar and understand how important it is, you'll feel more comfortable with the procedure and more in control of your disease. Testing is crucial because it tells you whether you're keeping your glucose levels in the range you and your doctor have agreed on.

The best range for you depends on your age and the type of diabetes you have. For younger adults who don't have complications of diabetes, a typical target range might be 80 to 120 mg/dL before meals, and below 180 mg/dL after eating. Older adults who have complications from their disease may have a fasting target goal of 100 to 140 mg/dL and below 200 mg/dL after meals. That's because blood sugar that falls too low in older adults can be more dangerous than in younger people.

How often you test your blood sugar depends on the type of diabetes you have. If you take insulin, test your blood sugar at least twice a day, and preferably three or four times a day. But if you have type 2 diabetes and don't use insulin, you may need to test your blood sugar levels only once a day or as little as twice a week.

Keep in mind that the amount of sugar in your blood is constantly changing. Self-monitoring helps you learn what makes your blood sugar levels rise and fall, so you can make adjustments in your treatment. Factors that affect your blood sugar include:

• Food. Food raises your blood sugar level ? it's highest one to two hours after a meal. What and how much you eat, and the time of day, also affect your blood sugar level.

• Exercise and physical activity. In general, the more active you are, the lower your blood sugar. Physical activity causes sugar to be transported to your cells, where it's used for energy, thereby lowering the levels in your blood. Aerobic exercises such as brisk walking, jogging or biking are especially good. But gardening, housework and even just being on your feet all day also can lower your blood sugar.

• Medications. Insulin and oral diabetes medications deliberately work to lower your blood sugar. But medications you take for other conditions may affect glucose levels. Corticosteroids, in particular, may raise blood sugar levels. Medications such as thiazides, used to control high blood pressure, and niacin, used for high cholesterol, also may increase blood sugar. If you need to take certain high blood pressure medications, your doctor will likely make changes in your diabetes treatment.

• Illness. The physical stress of a cold or other illness causes your body to produce hormones that raise your blood sugar level. The additional sugar helps promote healing. But if you have diabetes, this can be a problem. In addition, a fever increases your metabolism and how quickly sugar is utilized, which can alter the amount of insulin you need. For these reasons, be sure to monitor your glucose levels frequently when you're sick.

• Alcohol. Even a small amount of alcohol ? about 2 ounces ? can cause your sugar levels to fall too low. But sometimes alcohol can cause sugar levels to rise. If you choose to drink, do so only in moderation. And monitor your blood sugar before and after consuming alcohol to see how it affects you. Also, keep in mind that alcohol counts as carbohydrate calories in your diet.

• Fluctuations in hormone levels. The female hormone estrogen typically makes cells more responsive to insulin, and progesterone makes cells more resistant. Although these two hormones fluctuate throughout the menstrual cycle, the majority of women don't notice a corresponding change in blood sugar levels. Those who do are more likely to experience changes in blood sugar during the third week of their menstrual cycle, when estrogen and progesterone levels are highest.

Hormone levels also fluctuate during perimenopause ? the time before menopause. How this affects blood sugar varies, but most women can control any symptoms with additional exercise and changes in their diet. If your symptoms are more severe, your doctor may recommend oral contraceptives or hormone replacement therapy (HRT). After menopause, many women with diabetes require about 20 percent less medication because their cells are more sensitive to insulin.

A healthy diet

Contrary to popular myth, there's no "diabetes diet." Furthermore, having diabetes doesn't mean you have to eat only bland, boring foods. Instead, it means you'll eat more fruits, vegetables and whole grains ? foods that are high in nutrition and low in fat and calories ? and fewer animal products and sweets. Actually, it's the same eating plan all Americans should follow.

Yet understanding what and how much to eat can be a challenging task. Fortunately, a registered dietitian can help you put together a meal plan that fits your health goals, food preferences and lifestyle. Once you've decided on a meal plan, keep in mind that consistency is extremely important. To keep your blood sugar at a consistent level, try to eat the same amount of food with the same proportion of carbohydrates, proteins and fats at the same time every day.

But even with all the information you need and the best intentions, sticking to your diet can be one of the most challenging parts of living with diabetes. The key is to find ways to stay motivated. Don't let others undermine your determination to eat in the healthiest way possible. You have to believe that what you're doing matters ? and that you're worth it.