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Insulin resistance denotes decreased sensitivity of target cells (muscle, fat cells) to insulin. It is the metabolic cause of the very common " metabolic syndrome", which is the clustering of diabetes mellitus (type 2), hypertension, combined hyperlipidemia and central obesity in patients. It also underlies most processes behind the metabolic complications of polycystic ovarian syndrome (PCOS).
In a normal person, a small amount of insulin is produced after eating ("postprandial"), and it signals the body to absorb the sugars from the food at a steady rate. In an "insulin resistant" person the message does not get to the cells so the sugar remains in the blood for long periods of time while ever more insulin is released in an attempt to trigger the sugar-uptake. The sugar circulates in the blood for several hours and then is taken into the cells very rapidly, leading to a steep drop in blood sugar and a hypoglycaemic reaction several hours after the meal.
At a later stage, frank hyperglycemia develops as pancreaticThe pancreas is a retroperitoneal organ that serves two functions: exocrine it produces pancreatic juice containing digestive enzymes endocrine it produces several important hormones Anatomy The pancreas is a retroperitoneal organ located posterior to the β-cellsBeta cells are a type of cell in the pancreas in areas called the islets of Langerhans. Beta cells make and release insulin, a hormone that controls the level of glucose (sugar) in the blood. There are two types of insulin production in beta cells: baseli are unable to produce adequate insulin to maintain normal blood sugar levels ("euglycemia").
During this test, which is generally used to diagnose diabetes mellitus type 2, the patient (who has been fasting) takes a fixed oral dose of glucose, and glucose levels are measured by fingerprick testing every 30 minutes of the following hours.
Interpretation depends on local guidelines, but glycemia exceeding 10 mmol/l is often diagnostic for diabetes.
OGTT can be normal or mildly abnormal in simple insulin resistance. Often, there are raised glucose levels in the early measurements, reflecting the loss of a postprandial (after the meal) peak in insulin production. Extension of the testing (for several more hours) will often reveal a hypoglycemicHypoglycemia is a medical term referring to a pathologic state produced and usually defined by a lower than normal amount of sugar ( glucose) in the blood. The term hypoglycemia literally means low blood sugar. Hypoglycemia can produce a variety of sympto "dip", which is a result of an overshoot in insulin production after the failure of the physiologic postprandial insulin response.
The gold standardA gold standard is the "best" test to determine whether something exists or not. The term gold standard is commonly used in medicine to distinguish the one test that identifies whether an individual has a disease process or not. An ideal gold standard tes for investigating and quantifying insulin resistance is the "hyperinsulinemic euglycemic clamp", so called because it measures the amount of glucose necessary to compensate for an increased insulin level without causing hypoglycemia. This was first reported by DeFronzo et al in 1979. The test is rarely performed in clinical care, but is sometimes used in medical research - for example, to assess the effects of different medications.
The procedure takes about 2 hours. Through a peripheral vein , insulin is infused at 0.06 units per kg body weight per minute. In order to compensate for the insulin infusion, glucose 20% is infused to maintain blood sugar levels between 5 and 5.5 mmol/l. The rate of glucose infusion is determined by checking the blood sugar levels every 5 minutes.
The rate of glucose infusion during the last 30 minutes of the test determines insulin sensitivity. If high levels (7.5 mg/min or higher) are required, the patient is insulin-sensitive. Very low levels (4.0 mg/min or lower) suggest that the body is resistant to insulin action. Levels between 4.1 and 7.4 mg/min are indetermined and might point at "impaired glucose tolerance", considered an early form of insulin resistance.