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Insulin Resistance and Pre-diabetes


What is insulin resistance?

Insulin resistance is a condition in which the body produces insulin but does not use it properly. Insulin, a hormone made by the pancreas, helps the body use glucose for energy. Glucose is a form of sugar that is the body’s main source of energy.

The body’s digestive system breaks food down into glucose, which then travels in the bloodstream to cells throughout the body. Glucose in the blood is called blood glucose, also known as blood sugar. As the blood glucose level rises after a meal, the pancreas releases insulin to help cells take in and use the glucose.

When people are insulin resistant, their muscle, fat, and liver cells do not respond properly to insulin. As a result, their bodies need more insulin to help glucose enter cells. The pancreas tries to keep up with this increased demand for insulin by producing more. Eventually, the pancreas fails to keep up with the body’s need for insulin. Excess glucose builds up in the bloodstream, setting the stage for diabetes. Many people with insulin resistance have high levels of both glucose and insulin circulating in their blood at the same time.

Insulin resistance increases the chance of developing type 2 diabetes and heart disease. Learning about insulin resistance is the first step toward making lifestyle changes that can help prevent diabetes and other health problems.
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What causes insulin resistance?

Scientists have identified specific genes that make people more likely to develop insulin resistance and diabetes. Excess weight and lack of physical activity also contribute to insulin resistance.

Many people with insulin resistance and high blood glucose have other conditions that increase the risk of developing type 2 diabetes and damage to the heart and blood vessels, also called cardiovascular disease. These conditions include having excess weight around the waist, high blood pressure, and abnormal levels of cholesterol and triglycerides in the blood. Having several of these problems is called metabolic syndrome or insulin resistance syndrome, formerly called syndrome X.
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Metabolic Syndrome

Metabolic syndrome is defined as the presence of any three of the following conditions:

  • waist measurement of 40 inches or more for men and 35 inches or more for women
  • triglyceride levels of 150 milligrams per deciliter (mg/dL) or above, or taking medication for elevated triglyceride levels
  • HDL, or “good,” cholesterol level below 40 mg/dL for men and below 50 mg/dL for women, or taking medication for low HDL levels
  • blood pressure levels of 130/85 or above, or taking medication for elevated blood pressure levels
  • fasting blood glucose levels of 100 mg/dL or above, or taking medication for elevated blood glucose levels

Source: Grundy SM, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation. 2005;112:2735–2752.
Similar definitions have been developed by the World Health Organization and the American Association of Clinical Endocrinologists.
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What is pre-diabetes?

PreDiabetesPre-diabetes is a condition in which blood glucose levels are higher than normal but not high enough for a diagnosis of diabetes. This condition is sometimes called impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), depending on the test used to diagnose it. The U.S. Department of Health and Human Services estimates that about one in four U.S. adults aged 20 years or older—or 57 million people—had pre-diabetes in 2007.

People with pre-diabetes are at increased risk of developing type 2 diabetes, formerly called adult-onset diabetes or noninsulin-dependent diabetes. 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 little or no insulin.

Studies have shown that most people with pre-diabetes develop type 2 diabetes within 10 years, unless they lose 5 to 7 percent of their body weight—about 10 to 15 pounds for someone who weighs 200 pounds—by making changes in their diet and level of physical activity. People with pre-diabetes also are at increased risk of developing cardiovascular disease.
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What are the symptoms of insulin resistance and pre-diabetes?

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

Health care providers use blood tests to determine whether a person has pre-diabetes but do not usually test for insulin resistance. Insulin resistance can be assessed by measuring the level of insulin in the blood. However, the test that most accurately measures insulin resistance, called the euglycemic clamp, is too costly and complicated to be used in most doctors’ offices. The clamp is a research tool used by scientists to learn more about glucose metabolism. If tests indicate pre-diabetes or metabolic syndrome, insulin resistance most likely is present.

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

  • Fasting glucose test. This test measures blood glucose in people who have not eaten anything for at least 8 hours. 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 IFG. People with IFG often have had insulin resistance for some time. They are much more likely to develop diabetes than people with normal blood glucose levels.
  • Glucose tolerance test. This test measures blood glucose after people fast for at least 8 hours and 2 hours after they drink a sweet liquid provided by a doctor or laboratory. A blood glucose level between 140 and 199 mg/dL means glucose tolerance is not normal but is not high enough for a diagnosis of diabetes. This form of pre-diabetes is called IGT and, like IFG, it points toward a history of insulin resistance and a risk for developing diabetes.

People whose test results indicate they have pre-diabetes should have their blood glucose levels checked again in 1 to 2 years.
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Risk Factors for Pre-diabetes and Type 2 Diabetes

The American Diabetes Association recommends that testing to detect pre-diabetes and type 2 diabetes be considered in adults without symptoms who are overweight or obese and have one or more additional risk factors for diabetes. In those without these risk factors, testing should begin at age 45.
Risk factors for pre-diabetes and diabetes—in addition to being overweight or obese or being age 45 or older—include the following:

  • being physically inactive
  • having a parent or sibling with diabetes
  • having a family background that is African American, Alaska Native, American Indian, Asian American, Hispanic/Latino, or Pacific Islander
  • giving birth to a baby weighing more than 9 pounds or being diagnosed with gestational diabetes—diabetes first found during pregnancy
  • having high blood pressure—140/90 or above—or being treated for high blood pressure
  • having an HDL, or “good,” cholesterol level below 35 mg/dL or a triglyceride level above 250 mg/dL
  • having polycystic ovary syndrome, also called PCOS
  • having impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) on previous testing
  • having other conditions associated with insulin resistance, such as severe obesity or acanthosis nigricans
  • having a history of cardiovascular disease

If test results are normal, testing should be repeated at least every 3 years. Health care providers may recommend more frequent testing depending on initial results and risk status.
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Can insulin resistance and pre-diabetes be reversed?

Yes. Physical activity and weight loss help the body respond better to insulin. By losing weight and being more physically active, people with insulin resistance or pre-diabetes may avoid developing type 2 diabetes.

The Diabetes Prevention Program (DPP) and other large studies have shown that people with pre-diabetes can often prevent or delay diabetes if they lose a modest amount of weight by cutting fat and calorie intake and increasing physical activity—for example, walking 30 minutes a day 5 days a week. Losing just 5 to 7 percent of body weight prevents or delays diabetes by nearly 60 percent. In the DPP, people aged 60 or older who made lifestyle changes lowered their chances of developing diabetes by 70 percent. Many participants in the lifestyle intervention group returned to normal blood glucose levels and lowered their risk for developing heart disease and other problems associated with diabetes. The DPP also showed that the diabetes drug metformin reduced the risk of developing diabetes by 31 percent.

People with insulin resistance or pre-diabetes can help their body use insulin normally by being physically active, making wise food choices, and reaching and maintaining a healthy weight. Physical activity helps muscle cells use blood glucose for energy by making the cells more sensitive to insulin.
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Body Mass Index (BMI)

BMI is a measurement of body weight relative to height. Adults aged 20 or older can use the BMI table below to find out whether they are normal weight, overweight, obese, or extremely obese. To use the table, follow these steps:

  • Find the person’s height in the left-hand column.
  • Move across the row to the number closest to that person’s weight.
  • Check the number at the top of that column.

The number at the top of the column is the person’s BMI. The words above the BMI number indicate whether the person is normal weight, overweight, obese, or extremely obese. People who are overweight, obese, or extremely obese should consider talking with a doctor about ways to lose weight to reduce the risk of diabetes.

The BMI table has certain limitations. It may overestimate body fat in athletes and others who have a muscular build and underestimate body fat in older adults and others who have lost muscle. BMI for children and teens must be determined based on age and sex in addition to height and weight. Information about BMI in children and teens, including a BMI calculator, is available from the Centers for Disease Control and Prevention (CDC) at www.cdc.gov/nccdphp/dnpa/bmi. The CDC website also has a BMI calculator for adults.

Body Mass Index Table

Printer-friendly version (pdf)


Body Mass Index Table 1 of 2

 

Normal

Overweight

Obese

BMI

19

20

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

Height
(inches)

Body Weight (pounds)

58

91

96

100

105

110

115

119

124

129

134

138

143

148

153

158

162

167

59

94

99

104

109

114

119

124

128

133

138

143

148

153

158

163

168

173

60

97

102

107

112

118

123

128

133

138

143

148

153

158

163

168

174

179

61

100

106

111

116

122

127

132

137

143

148

153

158

164

169

174

180

185

62

104

109

115

120

126

131

136

142

147

153

158

164

169

175

180

186

191

63

107

113

118

124

130

135

141

146

152

158

163

169

175

180

186

191

197

64

110

116

122

128

134

140

145

151

157

163

169

174

180

186

192

197

204

65

114

120

126

132

138

144

150

156

162

168

174

180

186

192

198

204

210

66

118

124

130

136

142

148

155

161

167

173

179

186

192

198

204

210

216

67

121

127

134

140

146

153

159

166

172

178

185

191

198

204

211

217

223

68

125

131

138

144

151

158

164

171

177

184

190

197

203

210

216

223

230

69

128

135

142

149

155

162

169

176

182

189

196

203

209

216

223

230

236

70

132

139

146

153

160

167

174

181

188

195

202

209

216

222

229

236

243

71

136

143

150

157

165

172

179

186

193

200

208

215

222

229

236

243

250

72

140

147

154

162

169

177

184

191

199

206

213

221

228

235

242

250

258

73

144

151

159

166

174

182

189

197

204

212

219

227

235

242

250

257

265

74

148

155

163

171

179

186

194

202

210

218

225

233

241

249

256

264

272

75

152

160

168

176

184

192

200

208

216

224

232

240

248

256

264

272

279

76

156

164

172

180

189

197

205

213

221

230

238

246

254

263

271

279

287



Body Mass Index Table 2 of 2

 

Obese

Extreme Obesity

BMI

36

37

38

39

40

41

42

43

44

45

46

47

48

49

50

51

52

53

54

Height
(inches)

Body Weight (pounds)

58

172

177

181

186

191

196

201

205

210

215

220

224

229

234

239

244

248

253

258

59

178

183

188

193

198

203

208

212

217

222

227

232

237

242

247

252

257

262

267

60

184

189

194

199

204

209

215

220

225

230

235

240

245

250

255

261

266

271

276

61

190

195

201

206

211

217

222

227

232

238

243

248

254

259

264

269

275

280

285

62

196

202

207

213

218

224

229

235

240

246

251

256

262

267

273

278

284

289

295

63

203

208

214

220

225

231

237

242

248

254

259

265

270

278

282

287

293

299

304

64

209

215

221

227

232

238

244

250

256

262

267

273

279

285

291

296

302

308

314

65

216

222

228

234

240

246

252

258

264

270

276

282

288

294

300

306

312

318

324

66

223

229

235

241

247

253

260

266

272

278

284

291

297

303

309

315

322

328

334

67

230

236

242

249

255

261

268

274

280

287

293

299

306

312

319

325

331

338

344

68

236

243

249

256

262

269

276

282

289

295

302

308

315

322

328

335

341

348

354

69

243

250

257

263

270

277

284

291

297

304

311

318

324

331

338

345

351

358

365

70

250

257

264

271

278

285

292

299

306

313

320

327

334

341

348

355

362

369

376

71

257

265

272

279

286

293

301

308

315

322

329

338

343

351

358

365

372

379

386

72

265

272

279

287

294

302

309

316

324

331

338

346

353

361

368

375

383

390

397

73

272

280

288

295

302

310

318

325

333

340

348

355

363

371

378

386

393

401

408

74

280

287

295

303

311

319

326

334

342

350

358

365

373

381

389

396

404

412

420

75

287

295

303

311

319

327

335

343

351

359

367

375

383

391

399

407

415

423

431

76

295

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, National Institutes of Health, 1998.
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Can medicines help reverse insulin resistance or pre-diabetes?

Clinical trials have shown that people at high risk for developing diabetes can be given treatments that delay or prevent onset of diabetes. The first therapy should always be an intensive lifestyle modification program because weight loss and physical activity are much more effective than any medication at reducing diabetes risk.

Several drugs have been shown to reduce diabetes risk to varying degrees. No drug is approved by the U.S. Food and Drug Administration to treat insulin resistance or pre-diabetes or to prevent type 2 diabetes. The American Diabetes Association recommends that metformin is the only drug that should be considered for use in diabetes prevention. Other drugs that have delayed diabetes have side effects or haven’t shown long-lasting benefit. Metformin use was recommended only for very high-risk individuals who have both forms of pre-diabetes (IGT and IFG), have a BMI of at least 35, and are younger than age 60. In the DPP, metformin was shown to be most effective in younger, heavier patients.
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Points to Remember

  • Insulin resistance is a condition in which the body’s cells do not use insulin properly. Insulin helps cells use blood glucose for energy.
  • Insulin resistance increases the risk of developing pre-diabetes, type 2 diabetes, and cardiovascular disease.
  • Pre-diabetes is a condition in which blood glucose levels are higher than normal but not high enough for a diagnosis of diabetes.
  • Causes of insulin resistance and pre-diabetes include genetic factors, excess weight, and lack of physical activity.
  • Being physically active, making wise food choices, and reaching and maintaining a healthy weight can help prevent or reverse insulin resistance and pre-diabetes.
  • The Diabetes Prevention Program (DPP) study confirmed that people at risk for developing type 2 diabetes can prevent or delay the onset of diabetes by losing 5 to 7 percent of their body weight through regular physical activity and a diet low in fat and calories.

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Hope through Research

Researchers continue to follow DPP participants to learn about the long-term effects of the study. Other research sponsored by the National Institutes of Health builds on the findings from the DPP, including research focusing on lowering diabetes risk in children. Once considered an adult disease, type 2 diabetes is becoming more common in children, and researchers are seeking ways to reverse this trend.

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) sponsors the HEALTHY study, which is part of a broad research initiative called STOPP T2D (Studies to Treat or Prevent Pediatric Type 2 Diabetes). The study seeks to improve the treatment and prevention of type 2 diabetes in youth, exploring the roles of nutrition, physical activity, and behavior change in lowering risk for type 2 diabetes in children. The participating 42 middle schools are randomly assigned to a program group implementing changes or a comparison group. Students in the program group have healthier choices from the cafeteria and vending machines; longer, more intense periods of physical activity; and activities and awareness campaigns that promote long-term healthy behaviors. Results from the HEALTHY study are expected in 2009.

The NIDDK also sponsors the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study, which focuses on treatment of type 2 diabetes in children and teens at 13 sites. The TODAY study will evaluate the effects of three treatment approaches on control of blood glucose levels, insulin production, insulin resistance, and other outcomes. Each approach involves medication, but one of the three treatment groups will also receive an intensive lifestyle intervention to help the participants lose weight and increase physical fitness.

More information about the TODAY study is available at www.todaystudy.org.
Participants in clinical trials can play a more active role in their own health care, gain access to new research treatments before they are widely available, and help others by contributing to medical research. For information about current studies, visit www.ClinicalTrials.gov.
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For More Information

For more information about the DPP and the risk of developing diabetes, see these publications:

These publications are available at www.diabetes.niddk.nih.gov or by calling 1–800–860–8747.

American Diabetes Association
1701 North Beauregard Street
Alexandria, VA 22311
Phone: 1–800–DIABETES (342–2383)
Email: AskADA@diabetes.org
Internet: www.diabetes.org

National Diabetes Education Program
1 Diabetes Way
Bethesda, MD 20814–9692
Phone: 1–888–693–NDEP (6337)
TTY: 1–866–569–1162
Fax: 703–738–4929
Email: ndep@mail.nih.gov
Internet: www.ndep.nih.gov

National Heart, Lung, and Blood Institute Information Center
P.O. Box 30105
Bethesda, MD 20824–0105
Phone: 301–592–8573
Fax: 301–592–8563
Email: nhlbiinfo@nhlbi.nih.gov
Internet: www.nhlbi.nih.gov

You may also find additional information about this topic by visiting MedlinePlus at www.medlineplus.gov.
This publication may contain information about medications. When prepared, this publication included the most current information available. For updates or for questions about any medications, contact the U.S. Food and Drug Administration toll-free at 1–888–INFO–FDA (1–888–463–6332) or visit www.fda.gov. Consult your doctor for more information.

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National Diabetes Information Clearinghouse

1 Information Way
Bethesda, MD 20892–3560
Phone: 1–800–860–8747
TTY: 1–866–569–1162
Fax: 703–738–4929
Email: ndic@info.niddk.nih.gov
Internet: www.diabetes.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 of 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. The 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 publication was originally 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 publication is not copyrighted. The Clearinghouse encourages users of this publication to duplicate and distribute as many copies as desired.

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