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Insulin Resistance Syndrome

Insulin resistance leads to a constellation of clinical findings including abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, glucose intolerance, and proinflammatory and prothrombotic states. Various experts have referred to this group of abnormalities as the Metabolic Syndrome, Dysmetabolic Syndrome (ICD-9 code 277.7), Syndrome X and Insulin Resistance Syndrome. It is important to recognize this syndrome because it is a risk factor for both cardiovascular disease (CVD) and type 2 diabetes.

The prevalence of insulin resistance is increased in nondiabetic individuals with the following medical history:

• Diagnosis of CVD, essential hypertension, polycystic ovarian syndrome, nonalcoholic steatohepatitis or acanthosis nigricans
• Family history of type 2 diabetes, hypertension or CVD
• History of gestational diabetes or glucose intolerance
• Non-caucasian ethnicity, especially Hispanic and South Asian
• Sedentary lifestyle
• Abdominal obesity
• Age >40 years
• Treatment with corticosteroids, antidepressants, antipsychotics, antihistamines, HIV protease inhibitors

Unfortunately, no single laboratory test is diagnostic of the insulin resistance syndrome. At least 3 professional organizations have published laboratory criteria for the diagnosis of this syndrome including the American Association of Clinical Endocrinologists (AACE), National Cholesterol Education Program’s Adult Treatment Panel III (ATP III), and the World Health Organization (WHO) (Circulation 2004;109:433-438 & 551-556 and Endocrine Practice 2003;9:240-52).

 

 

The major difference between these criteria is in the tests for glucose intolerance. Both the AACE and WHO recommend an oral glucose tolerance test (OGTT), even in patients without an elevated fasting glucose. ATP III does not recommend OGTT in such persons, because they believe that the increased sensitivity does not outweigh the increased cost and inconvenience. WHO includes elevated microalbumin in their diagnostic criteria, but the other 2 organizations do not.

ATP III requires 3 of 5 abnormalities for diagnosis of insulin resistance syndrome. WHO requires evidence of glucose intolerance plus 2 more abnormalities. AACE does not specify a defined number of abnormalities and leaves the diagnosis to clinical judgment.

Even though hyperinsulinemia plays a central role in the pathogenesis of the Insulin Resistance Syndrome, none of the organizations includes measurement of plasma insulin in their diagnostic criteria. The main reason for this omission is that methods to quantify insulin are not standardized and values obtained in different laboratories are not comparable. Also, the absolute difference in values between insulin sensitive and insulin resistant individuals is small and a diagnostic cutoff point has not been established. Finally, no one has demonstrated that an increase in insulin concentration, by itself, can predict the development of CVD.

Although they are not included in the diagnostic criteria, other laboratory tests may be abnormal in individuals with insulin resistance. Examples include increased plasma uric acid, decreased renal uric acid clearance, increased plasminogen activator inhibitor 1, increased fibrinogen, elevated high sensitivity C reactive protein, and increased WBC count.