Insulin Resistance and Pre-Diabetes

 

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.

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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. In a cross-section of U.S. adults aged 40 to 74 tested during the period 1988 to 1994, 33.8 percent had IFG, 15.4 percent had IGT, and 40.1 percent had pre-diabetes (IGT or IFG or both). Applying these percentages to the 2000 U.S. population, about 35 million adults aged 40 to 74 would have IFG, 16 million would have IGT, and 41 million would have pre-diabetes.

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.

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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.

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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.

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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.


 

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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.
* pdf versions require the free Adobe® Acrobat Reader software for viewing.

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

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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.

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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.

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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.

This e-text is not copyrighted. The clearinghouse encourages users of this e-pub to duplicate and distribute as many copies as desired.


NIH Publication No. 04-4893
May 2004

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