Insulin resistance and Pre-Diabetes

What does insulin do?
How are insulin resistance, pre-diabetes, and type 2 diabetes linked?
What causes insulin resistance?
What are the symptoms of insulin resistance and pre-diabetes?
Do you have insulin resistance or pre-diabetes?
Can you reverse insulin resistance?
Be Active and Eat Well
Stop Smoking
Can medicines help?

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 (IFG) or impaired glucose tolerance (IGT), depending on the test used to diagnose it. Pre-diabetes is becoming more common in the United States, according to new estimates provided by the U.S. Department of Health and Human Services. About 40 percent of U.S. adults ages 40 to 74—or 41 million people—had prediabetes in 2000. New data suggest that at least 54 million U.S. adults had pre-diabetes in 2002.

If you have pre-diabetes, you have a higher risk of developing type 2 diabetes, formerly called adultonset diabetes or noninsulin-dependent diabetes. Studies have shown that most people with prediabetes 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).

Metabolic Syndrome

Metabolic syndrome is defined by the National Cholesterol Education Program as 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.

Note: Other definitions of similar conditions have been developed by the World Health Organization and
the Association of
Clinical Endocrinologists.

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?
Anyone 45 years or older should consider getting tested for diabetes. If you are overweight and aged 45 or older, it is strongly recommended that you get tested. You should consider getting tested if you are younger than 45, overweight, and 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 100 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, 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 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.

If your blood glucose is higher than normal but lower than the diabetes range, have your blood glucose checked in 1 to 2 years.

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 100 mg/dL. If it is in
    the 100 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.

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 Body Mass Index Table 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.

Body Mass Index Table

For a printer-friendly version of this table, use the pdf.*
Normal Overweight Obese
BMI 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36
Height (inches) Body Weight (pounds)
58 91 96 100 105 110 115 119 124 129 134 138 143 148 153 158 162 167 172
59 94 99 104 109 114 119 124 128 133 138 143 148 153 158 163 168 173 178
60 97 102 107 112 118 123 128 133 138 143 148 153 158 163 168 174 179 184
61 100 106 111 116 122 127 132 137 143 148 153 158 164 169 174 180 185 190
62 104 109 115 120 126 131 136 142 147 153 158 164 169 175 180 186 191 196
63 107 113 118 124 130 135 141 146 152 158 163 169 175 180 186 191 197 203
64 110 116 122 128 134 140 145 151 157 163 169 174 180 186 192 197 204 209
65 114 120 126 132 138 144 150 156 162 168 174 180 186 192 198 204 210 216
66 118 124 130 136 142 148 155 161 167 173 179 186 192 198 204 210 216 223
67 121 127 134 140 146 153 159 166 172 178 185 191 198 204 211 217 223 230
68 125 131 138 144 151 158 164 171 177 184 190 197 203 210 216 223 230 236
69 128 135 142 149 155 162 169 176 182 189 196 203 209 216 223 230 236 243
70 132 139 146 153 160 167 174 181 188 195 202 209 216 222 229 236 243 250
71 136 143 150 157 165 172 179 186 193 200 208 215 222 229 236 243 250 257
72 140 147 154 162 169 177 184 191 199 206 213 221 228 235 242 250 258 265
73 144 151 159 166 174 182 189 197 204 212 219 227 235 242 250 257 265 272
74 148 155 163 171 179 186 194 202 210 218 225 233 241 249 256 264 272 280
75 152 160 168 176 184 192 200 208 216 224 232 240 248 256 264 272 279 287
76 156 164 172 180 189 197 205 213 221 230 238 246 254 263 271 279 287 295
Obese Extreme Obesity
BMI 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54
Height
(inches)
Body Weight (pounds)
58 177 181 186 191 196 201 205 210 215 220 224 229 234 239 244 248 253 258
59 183 188 193 198 203 208 212 217 222 227 232 237 242 247 252 257 262 267
60 189 194 199 204 209 215 220 225 230 235 240 245 250 255 261 266 271 276
61 195 201 206 211 217 222 227 232 238 243 248 254 259 264 269 275 280 285
62 202 207 213 218 224 229 235 240 246 251 256 262 267 273 278 284 289 295
63 208 214 220 225 231 237 242 248 254 259 265 270 278 282 287 293 299 304
64 215 221 227 232 238 244 250 256 262 267 273 279 285 291 296 302 308 314
65 222 228 234 240 246 252 258 264 270 276 282 288 294 300 306 312 318 324
66 229 235 241 247 253 260 266 272 278 284 291 297 303 309 315 322 328 334
67 236 242 249 255 261 268 274 280 287 293 299 306 312 319 325 331 338 344
68 243 249 256 262 269 276 282 289 295 302 308 315 322 328 335 341 348 354
69 250 257 263 270 277 284 291 297 304 311 318 324 331 338 345 351 358 365
70 257 264 271 278 285 292 299 306 313 320 327 334 341 348 355 362 369 376
71 265 272 279 286 293 301 308 315 322 329 338 343 351 358 365 372 379 386
72 272 279 287 294 302 309 316 324 331 338 346 353 361 368 375 383 390 397
73 280 288 295 302 310 318 325 333 340 348 355 363 371 378 386 393 401 408
74 287 295 303 311 319 326 334 342 350 358 365 373 381 389 396 404 412 420
75 295 303 311 319 327 335 343 351 359 367 375 383 391 399 407 415 423 431
76 304 312 320 328 336 344 353 361 369 377 385 394 402 410 418 426 435 443

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

  • 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” holesterol. 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. You will reduce your risk for respiratory problems, lung cancer, and diabetes.

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. Alpha-glucosidase 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

Researchers sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases conducted the DPP to find the most effective ways to prevent or delay the onset of type 2 diabetes. Volunteers were recruited from groups known to be at particularly high risk for IGT and type 2 diabetes. The study was designed to compare the effectiveness of lifestyle changes (weight loss through exercise and diet) with drug therapy (metformin). A control group received a placebo and information on diet and exercise. Participants assigned to the 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 demonstrates that a healthy diet and exercise are the most effective treatment for insulin resistance and the prediabetic states of IFG and IGT.

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 stepping-stone 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.

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National Diabetes Information Clearinghouse
1 Information Way
Bethesda, MD 20892-3570
Email: ndic@info.niddk.nih.gov

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.

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U.S. Department of Health and Human Services
National Institutes of Health

NIH Publication No. 04-4893
August 2006