Insulin resistance and pre-diabetes.

National Diabetes Information Clearinghouse

Insulin resistance is a silent condition that increases the chances of developing diabetes and heart disease. Learning about insulin resistance is the first step you can take toward making lifestyle changes that will help you prevent diabetes and other health problems.

What does insulin do?

After you eat, the food is broken down into glucose, the simple sugar that is the main source of energy for the body's cells. But your cells cannot use glucose without insulin, a hormone produced by the pancreas. Insulin helps the cells take in glucose and convert it to energy. When the pancreas does not make enough insulin or the body is unable to use the insulin that is present, the cells cannot use glucose. Excess glucose builds up in the bloodstream, setting the stage for diabetes.

Being obese or overweight affects the way insulin works in your body. Extra fat tissue can make your body resistant to the action of insulin, but exercise helps insulin work well.

How are insulin resistance, pre-diabetes, and type 2 diabetes linked?

If you have insulin resistance, your muscle, fat, and liver cells do not use insulin properly. The pancreas tries to keep up with the demand for insulin by producing more. Eventually, the pancreas cannot keep up with the body's need for insulin, and excess glucose builds up in the bloodstream. Many people with insulin resistance have high levels of blood glucose and high levels of insulin circulating in their blood at the same time.

People with blood glucose levels that are higher than normal but not yet in the diabetic range have "pre-diabetes." Doctors sometimes call this condition impaired fasting glucose or impaired glucose tolerance, depending on the test used to diagnose it. About 16 million people in the United States have pre-diabetes and most don't know it.

If you have pre-diabetes, you have a higher risk of developing type 2 diabetes, formerly called adult-onset diabetes or noninsulin-dependent diabetes. Studies have shown that most people with pre-diabetes go on to develop type 2 diabetes within 10 years, unless they lose 5 to 7 percent of their body weight--which is about 10 to 15 pounds for someone who weighs 200 pounds--by making modest changes in their diet and level of physical activity. People with pre-diabetes also have a higher risk of heart disease.

Type 2 diabetes is sometimes defined as the form of diabetes that develops when the body does not respond properly to insulin, as opposed to type 1 diabetes, in which the pancreas makes no insulin at all. At first, the pancreas keeps up with the added demand by producing more insulin. In time, however, it loses the ability to secrete enough insulin in response to meals.

Insulin resistance can also occur in people who have type 1 diabetes, especially if they are overweight.

What causes insulin resistance?

Because insulin resistance tends to run in families, we know that genes are partly responsible. Excess weight also contributes to insulin resistance because too much fat interferes with muscles' ability to use insulin. Lack of exercise further reduces muscles' ability to use insulin.

Many people with insulin resistance and high blood glucose have excess weight around the waist, high LDL (bad) blood cholesterol levels, low HDL (good) cholesterol levels, high levels of triglycerides (another fat in the blood), and high blood pressure, all conditions that also put the heart at risk. This combination of problems is referred to as the metabolic syndrome, or the insulin resistance syndrome (formerly called Syndrome X).

What are the symptoms of insulin resistance and pre-diabetes?

Insulin resistance and pre-diabetes usually have no symptoms. You may have one or both conditions for several years without noticing anything. If you have a severe form of insulin resistance, you may get dark patches of skin, usually on the back of your neck. Sometimes people get a dark ring around their neck. Other possible sites for these dark patches include elbows, knees, knuckles, and armpits. This condition is called acanthosis nigricans.

If you have a mild or moderate form of insulin resistance, blood tests may show normal or high blood glucose and high levels of insulin at the same time.

Do you have insulin resistance or pre-diabetes?

If you are overweight and age 45 or older, you should ask your doctor about having one of the standard blood glucose tests that detect pre-diabetes and type 2 diabetes. If you are younger than 45 and overweight, your doctor may want to test your blood glucose, especially if you have one or more of the following risk factors:

* family history of diabetes

* low HDL cholesterol and high triglycerides

* high blood pressure

* history of gestational diabetes (diabetes during pregnancy) or gave birth to a baby weighing more than 9 pounds

* minority group background (African American, American Indian, Hispanic American/Latino, or Asian American/ Pacific Islander)

Diabetes and pre-diabetes can be detected with one of the following tests:

A fasting glucose test measures your blood glucose after you have gone overnight without eating. This test is most reliable when done in the morning. Fasting glucose levels of 110 to 125 mg/dL are above normal but not high enough to be called diabetes. This condition is called pre-diabetes or impaired fasting glucose (IFG), and it suggests that you have probably had insulin resistance for some time. IFG is considered a pre-diabetic state, meaning that you are more likely to develop diabetes but do not have it yet.

A glucose tolerance test measures your blood glucose after an overnight fast and 2 hours after you drink a sweet liquid provided by the doctor or laboratory. If your blood glucose falls between 140 and 199 mg/dL 2 hours after drinking the liquid, your glucose tolerance is above normal but not high enough for diabetes. This condition, also a form of pre-diabetes, is called impaired glucose tolerance (IGT) and, like IFG, it points toward a history of insulin resistance and a risk for developing diabetes.

These tests give only indirect evidence of insulin resistance. The test that most accurately measures insulin resistance is too complicated and expensive to use as a screening tool in most doctors' offices. The test, called the euglycemic clamp, is a research tool that helps scientists learn more about sugar metabolism problems. Insulin resistance can also be assessed with measurement of fasting insulin. If conventional tests show that you have IFG or IGT, your doctor may suggest changes in diet and exercise to reduce your risk of developing diabetes.

Can you reverse insulin resistance?

Yes. Physical activity and weight loss make the body respond better to insulin. By losing weight and being more physically active, you may avoid developing type 2 diabetes. In fact, a major study has verified the benefits of healthy lifestyle changes and weight loss. In 2001, the National Institutes of Health completed the Diabetes Prevention Program (DPP), a clinical trial designed to find the most effective ways of preventing type 2 diabetes in overweight people with pre-diabetes. The researchers found that lifestyle changes reduced the risk of diabetes by 58 percent. Also, many people with pre-diabetes returned to normal blood glucose levels.

The main goal in treating insulin resistance and pre-diabetes is to help your body relearn to use insulin normally. You can do several things to help reach this goal.

Be Active and Eat Well

Physical activity helps your muscle cells use blood glucose because they need it for energy. Exercise makes those cells more sensitive to insulin.

The DPP confirmed that people who follow a low-fat, low-calorie diet and who increase activities such as walking briskly or riding a bike for 30 minutes, five times a week, have a far smaller risk of developing diabetes than people who do not exercise regularly. The DPP also reinforced the importance of a low-calorie, low-fat diet. Following a low-calorie, low-fat diet can provide two benefits. If you are overweight, one benefit is that limiting your calorie and fat intake can help you lose weight. DPP participants who lost weight were far less likely to develop diabetes than others in the study who remained at an unhealthy weight. Increasing your activity and following a low-calorie, low-fat diet can also improve your blood pressure and cholesterol levels and has many other health benefits.

Scientists have established some numbers to help people set goals that will reduce their risk of developing glucose metabolism problems.

* Weight. Body mass index (BMI) is a measure used to evaluate body weight relative to height. You can use BMI to find out whether you are underweight, normal weight, overweight, or obese. Use the table on page 5 to find your BMI.

--Find your height in the left-hand column.

--Move across in the same row to the number closest to your weight.

--The number at the top of that column is your BMI. Check the word above your BMI to see whether you are normal weight, overweight, or obese. If you are overweight or obese, talk with your doctor about ways to lose weight to reduce your risk of diabetes.

* Blood pressure. Blood pressure is expressed as two numbers that represent pressure in your blood vessels when your heart is beating (systolic pressure) and when it is resting (diastolic pressure). The numbers are usually written with a slash--for example, 140/90, which is expressed as "140 over 90." For the general population, blood pressure below 130/85 is considered normal, although people whose blood pressure is slightly elevated and who have no additional risk factors for heart disease may be advised to make lifestyle changes--that is, diet and exercise--rather than take blood pressure medicines. People who have diabetes, however, should take whatever steps necessary, including lifestyle changes and medicine, to reach a blood pressure goal of below 130/80.

* Cholesterol. Your cholesterol is usually reported with three values: low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, and total cholesterol. LDL cholesterol is sometimes called "bad" cholesterol, while HDL cholesterol is called "good" cholesterol. To lower your risk of cardiovascular problems if you have diabetes, you should try to keep your LDL cholesterol below 100 and your total cholesterol below 200.

If you have metabolic syndrome, your doctor may recommend weight loss with diet and exercise, as well as medication to lower your cholesterol and blood pressure levels.

Stop Smoking

In addition to increasing your risk of cancer and cardiovascular disease, smoking contributes to insulin resistance. Quitting smoking is not easy, but it could be the single smartest thing you can do to improve your health.

Can medicines help?

Two classes of drugs can improve response to insulin and are used by prescription for type 2 diabetes--biguanides and thiazolidinediones. Other medicines used for diabetes act by other mechanisms. Alphaglucosidase inhibitors restrict or delay the absorption of carbohydrates after eating, resulting in a slower rise of blood glucose levels. Sulfonylureas and meglitinides increase insulin production.

The DPP showed that the diabetes drug metformin, a biguanide, reduced the risk of diabetes in those with pre-diabetes but was much less successful than losing weight and increasing activity. In another study, treatment with troglitazone, a thiazolidinedione later withdrawn from the market following reports of liver toxicity, delayed or prevented type 2 diabetes in Hispanic women with a history of gestational diabetes. Acarbose, an alpha-glucosidase inhibitor, has been effective in delaying development of type 2 diabetes. Additional studies using other diabetes medicines and some types of blood pressure medicines to prevent diabetes are under way. No drug has been approved by the Food and Drug Administration (FDA) specifically for insulin resistance or pre-diabetes.

Hope Through Research

Research sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases and other components of the Public Health Service has clearly shown that people can do a lot to prevent or delay type 2 diabetes. Volunteers in the DPP were recruited from groups known to be at particularly high risk for type 2 diabetes. About 45 percent of the DPP volunteers were from minority groups known to be at high risk for diabetes. The study was designed to assess the effectiveness of lifestyle changes (weight loss through exercise and diet) and drug therapy (metformin). A control group received a placebo and information on diet and exercise. Participants assigned to intensive lifestyle intervention reduced their risk of getting type 2 diabetes by 58 percent over 3 years. Participants treated with metformin reduced their risk by 31 percent. Metformin is not currently approved for use in preventing diabetes, but the FDA may determine whether to make diabetes prevention an added indication for this drug. In any event, the DPP demonstrated that a healthy diet and exercise are the most effective treatment for insulin resistance and pre-diabetes.

Body Mass Index Table

                       Normal                       Overweight

BMI    19     20     21     22     23     24     25     26     27

Height                         Body Weight
(inches)                        (pounds)

58      91     96    100    105    110    115    119    124    129
59      94     99    104    109    114    119    124    128    133
60      97    102    107    112    118    123    128    133    138
61     100    106    111    116    122    127    132    137    143
62     104    109    115    120    126    131    136    142    147
63     107    113    118    124    130    135    141    146    152
64     110    116    122    128    134    140    145    151    157
65     114    120    126    132    138    144    150    156    162
66     118    124    130    136    142    148    155    161    167
67     121    127    134    140    146    153    159    166    172
68     125    131    138    144    151    158    164    171    177
69     128    135    142    149    155    162    169    176    182
70     132    139    146    153    160    167    174    181    188
71     136    143    150    157    165    172    179    186    193
72     140    147    154    162    169    177    184    191    199
73     144    151    159    166    174    182    189    197    204
74     148    155    163    171    179    186    194    202    210
75     152    160    168    176    184    192    200    208    216
76     156    164    172    180    189    197    205    213    221

       Overweight                        Obese

BMI    28     29     30     31     32     33     34     35     36

Height                         Body Weight
(inches)                        (pounds)

58     134    138    143    148    153    158    162    167    172
59     138    143    148    153    158    163    168    173    178
60     143    148    153    158    163    168    174    179    184
61     148    153    158    164    169    174    180    185    190
62     153    158    164    169    175    180    186    191    196
63     158    163    169    175    180    186    191    197    203
64     163    169    174    180    186    192    197    204    209
65     168    174    180    186    192    198    204    210    216
66     173    179    186    192    198    204    210    216    223
67     178    185    191    198    204    211    217    223    230
68     184    190    197    203    210    216    223    230    236
69     189    196    203    209    216    223    230    236    243
70     195    202    209    216    222    229    236    243    250
71     200    208    215    222    229    236    243    250    257
72     206    213    221    228    235    242    250    258    265
73     212    219    227    235    242    250    257    265    272
74     218    225    233    241    249    256    264    272    280
75     224    232    240    248    256    264    272    279    287
76     230    238    246    254    263    271    279    287    295

             Obese                 Extreme Obesity

BMI    37     38     39     40     41     42     43     44     45

Height                         Body Weight
(inches)                        (pounds)

58     177    181    186    191    196    201    205    210    215
59     183    188    193    198    203    208    212    217    222
60     189    194    199    204    209    215    220    225    230
61     195    201    206    211    217    222    227    232    238
62     202    207    213    218    224    229    235    240    246
63     208    214    220    225    231    237    242    248    254
64     215    221    227    232    238    244    250    256    262
65     222    228    234    240    246    252    258    264    270
66     229    235    241    247    253    260    266    272    278
67     236    242    249    255    261    268    274    280    287
68     243    249    256    262    269    276    282    289    295
69     250    257    263    270    277    284    291    297    304
70     257    264    271    278    285    292    299    306    313
71     265    272    279    286    293    301    308    315    322
72     272    279    287    294    302    309    316    324    331
73     280    288    295    302    310    318    325    333    340
74     287    295    303    311    319    326    334    342    350
75     295    303    311    319    327    335    343    351    359
76     304    312    320    328    336    344    353    361    369

                            Extreme Obesity

BMI    46     47     48     49     50     51     52     53     54

Height                         Body Weight
(inches)                        (pounds)

58     220    224    229    234    239    244    248    253    258
59     227    232    237    242    247    252    257    262    267
60     235    240    245    250    255    261    266    271    276
61     243    248    254    259    264    269    275    280    285
62     251    256    262    267    273    278    284    289    295
63     259    265    270    278    282    287    293    299    304
64     267    273    279    285    291    296    302    308    314
65     276    282    288    294    300    306    312    318    324
66     284    291    297    303    309    315    322    328    334
67     293    299    306    312    319    325    331    338    344
68     302    308    315    322    328    335    341    348    354
69     311    318    324    331    338    345    351    358    365
70     320    327    334    341    348    355    362    369    376
71     329    338    343    351    358    365    372    379    386
72     338    346    353    361    368    375    383    390    397
73     348    355    363    371    378    386    393    401    408
74     358    365    373    381    389    396    404    412    420
75     367    375    383    391    399    407    415    423    431
76     377    385    394    402    410    418    426    435    443

Source: Adapted from Clinical Guidelines on the Identification,
Evaluation, and Treatment of Overweight and Obesity in Adults: The
Evidence Report.

Metabolic Syndrome

Metabolic syndrome is the term researchers give to the presence of any three of the following conditions:

* excess weight around the waist (waist measurement of more than 40 inches for men and more than 35 inches for women)

* high levels of triglycerides (150 mg/dL or higher)

* low levels of HDL, or "good," cholesterol (below 40 mg/dL for men and below 50 mg/dL for women)

* high blood pressure (130/85 mm Hg or higher)

* high fasting blood glucose levels (110 mg/dL or higher)

Source: National Cholesterol Education Program, Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), National Heart, Lung, and Blood Institute, National Institutes of Health, May 2001.

Lab Tests and What They Show

* Blood glucose. High blood glucose may be a sign that your body does not have enough insulin or does not use it well. However, a fasting measurement or oral glucose tolerance test gives more precise information.

* Insulin. An insulin measurement helps determine whether a high blood glucose reading is the result of insufficient insulin or poor use of insulin.

* Fasting glucose. Your blood glucose level should be lower after several hours without eating. After an overnight fast, the normal level is below 110 mg/dL If it is in the 110 to 125 mg/dL range, you have impaired fasting glucose or pre-diabetes. A result of 126 or higher, if confirmed on a repeat test, indicates diabetes.

* Glucose tolerance. Your blood glucose level will be higher after drinking a sugar solution, but it should still be below 140 mg/dL 2 hours after the drink. If it is higher than normal (in the 140 to 199 mg/dL range) 2 hours after drinking the solution, you have IGT or pre-diabetes, which is another strong indication that your body has trouble using glucose. A level of 200 or higher, if confirmed, means diabetes is already present.

Points to Remember

* Glucose is the simple sugar that is the main source of energy for the body's cells.

* Insulin helps cells take in blood glucose and convert it to energy.

* If you have insulin resistance, your body's cells do not respond well to insulin.

* Insulin resistance is a steppingstone to type 2 diabetes.

* Lack of exercise and excess weight contribute to insulin resistance.

* Engaging in moderate physical activity and maintaining proper weight can help prevent insulin resistance.

* Insulin resistance plays a role in the development of cardiovascular disease, which damages the heart and blood vessels.

* Controlling blood pressure and LDL cholesterol and not smoking can also help prevent cardiovascular problems.

* The Diabetes Prevention Program confirmed that exercise and a low-calorie, low-fat diet are the best ways to prevent type 2 diabetes.

National Diabetes Information Clearinghouse

1 Information Way

Bethesda, MD 20892-3560

Phone: [phone] or [phone]

Fax: [phone]

Email: [e-mail]

The National Diabetes Information Clearinghouse (NDIC) is a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The NIDDK is part of the National Institutes of Health under the U.S. Department of Health and Human Services. Established in 1978, the clearinghouse provides information about diabetes to people with diabetes and to their families, health care professionals, and the public. NDIC answers inquiries, develops and distributes publications, and works closely with professional and patient organizations and Government agencies to coordinate resources about diabetes.

Publications produced by the clearinghouse are carefully reviewed by both NIDDK scientists and outside experts. This fact sheet was reviewed by George A. Bray, M.D., Pennington Biomedical Research Center, Louisiana State University; and Richard F. Hamman, M.D., Dr. P.H., Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center.