Insulin Resistance and Pre-Diabetes

• What is insulin resistance?
• What causes insulin resistance?
• Metabolic Syndrome
• What is pre-diabetes?
• What are the symptoms of insulin resistance and pre-diabetes?
• How are insulin resistance and pre-diabetes diagnosed?
• Risk Factors for Pre-diabetes and Type 2 Diabetes
• Can insulin resistance and pre-diabetes be reversed?
• Body Mass Index (BMI)
• Can medicines help reverse insulin resistance or pre-diabetes?
• Points to Remember

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?

Pre-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 year. 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

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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 Ambulatory Reversal Program 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.
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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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