On August 25-26, members of the American College of Endocrinology met in Washington D.C., where national and international experts addressed key questions about the causes, prevalence, assessment, prevention and treatment of the Insulin Resistance Syndrome. The following is a summary of the findings from that conference.
1. What is the Insulin Resistance Syndrome (IRS)?
The Insulin Resistance Syndrome describes a condition that is characterized by decreased tissue sensitivity to the action of insulin, leading to a compensatory increase in insulin secretion. This metabolic dysfunction leads to a cluster of abnormalities with serious clinical consequences, most importantly, cardiovascular disease and/or type 2 diabetes. The Insulin Resistance Syndrome Conference extended the concept of the Metabolic Syndrome (NCEP/ATP III) by:
1) Addressing the underlying pathophysiology of insulin resistance, which leads not only to cardiovascular disease, but also to diabetes and other disorders.
2) Recognizing additional associated disorders such as polycystic ovary syndrome (PCOS) and non-alcoholic fatty liver disease.
3) Improving the detection of the Insulin Resistance Syndrome by emphasizing the use of the 2-hour post glucose challenge as the most sensitive clinically available test for insulin resistance.
2. What is the clinical impact of the Insulin Resistance Syndrome?
One in three American adults has insulin resistance; most are able to produce enough insulin to maintain non-diabetic glucose levels. Many of these individuals will go on to develop overt type 2 diabetes, however the majority will not develop diabetes, but are still at significant increased risk for heart attack or stroke and other diseases. Over 80% of the 16 million Americans who have type 2 diabetes are insulin resistant. One in ten women have polycystic ovary syndrome, placing them at high risk for cardiovascular disease and type 2 diabetes -- two of the most costly and deadly diseases in the U.S. The current epidemic of obesity among children and adolescents puts them at risk for insulin resistance and its complications.
3. Who is more likely to have the Insulin Resistance Syndrome?
The more factors an individual has, the greater the likelihood of having the Insulin Resistance Syndrome.
Overweight: a Body Mass Index (BMI) > or = 25 kg/m2 or a waist circumference
of >40 inches for men, >35 inches for women
A sedentary lifestyle
Over age 40 years
Non-Caucasian ethnicity (e.g., Latino/Hispanic American, African
American, Native American, Asian American, Pacific Islander)
A family history of type 2 diabetes, hypertension or cardiovascular
disease
A history of glucose intolerance or gestational diabetes
A diagnosis of hypertension, elevated triglycerides/low HDL-cholesterol,
or cardiovascular disease
Acanthosis nigricans
Polycystic ovary syndrome
4. How can the Insulin Resistance Syndrome be detected in clinical practice?
Individuals at risk for having the Insulin Resistance Syndrome can be identified by history, physical examination and laboratory evaluation. The following are the characteristic abnormalities of the Insulin Resistance Syndrome. Standardized assays for plasma insulin are not generally available for routine clinical use. It is important to note that the post-glucose challenge provides a more sensitive indicator of insulin resistance than fasting plasma glucose measurement.
Plasma Glucose
Fasting: 110 - 125 mg/dL
120 min post-glucose challenge (75 g): > 140 mg/dL
Triglycerides* > 150 mg/dL
HDL cholesterol*
Men: < 40 mg/dL
Women: < 50 mg/dL
Blood pressure* > 130/> 85 mm Hg
* Levels based upon NCEP/ATP III Guidelines, JAMA, May 16, 2001.
5. What is a reasonable approach to managing the Insulin Resistance Syndrome in clinical practice?
A discussion of treatment considerations for patients with the Insulin Resistance Syndrome must begin by differentiating between efforts focused on improving insulin sensitivity itself and those aimed at treatment of any of the specific manifestations of the Insulin Resistance Syndrome.
Efforts to improve insulin sensitivity
There is consensus that individualized lifestyle modification is appropriate for all patients who are considered to have the Insulin Resistance Syndrome. The panel encourages research into other approaches, including pharmacologic therapies, to address insulin resistance.
Treatment of the components
Evidence-based guidelines exist which support the appropriate use of pharmacologic agents to treat the individual components of the Insulin Resistance Syndrome. Individuals identified as being at risk for the Insulin Resistance Syndrome should be followed closely, anticipating the development of complications.
6. What should be the priorities for the future?
The panel identified three key areas of particular interest.
1. Development of a better diagnostic test for insulin resistance.
2. Targeted testing for individuals and families at risk.
3. Research into pharmacologic therapies to improve insulin sensitivity.
Summary
The Insulin Resistance Syndrome Conference attempted to provide a means of understanding the Insulin Resistance Syndrome and a practical clinical approach to identifying and managing individuals at risk. By necessity, we had to limit discussion to outline form only, especially with regard to treatment. While we have accepted the lipid and blood pressure guidelines from ATP III, we do suggest certain differences from earlier excellent efforts to identify individuals who are insulin resistant and hyperinsulinemic, and at increased risk to develop type 2 diabetes and CVD. These differences may be summarized as follows:
1) The Insulin Resistance Syndrome is used to describe the cluster of abnormalities that are more likely to occur in insulin resistant/hyperinsulinemic individuals.
2) The Insulin Resistance Syndrome is differentiated from type 2 diabetes.
3) BMI, as well as waist circumference, is used as the index of obesity, and viewed as a physiological variable that increases insulin resistance, rather than as a criterion for diagnosis of the Insulin Resistance Syndrome.
4) Ethnicity is introduced as an important risk factor for insulin resistance, and non-Caucasian ancestry identified as increasing risk of the Insulin Resistance Syndrome.
5) Other factors have been identified that increase the risk of developing the Insulin Resistance Syndrome, including a family history of type 2 diabetes, hypertension, CVD, as well as a personal history of CVD, PCOS, gestational diabetes, and acanthosis nigricans.
6) Fasting plasma glucose concentration is used to identify individuals with type 2 diabetes, however, the plasma glucose concentration 2 hours after a 75 g oral glucose load is introduced as a more sensitive measure of risk for the Insulin Resistance Syndrome.
We are supportive of current concepts in medically supervised therapeutic lifestyle change, including concerns about high carbohydrate diets, efforts directed to the treatment of obesity, and strategies for increasing physical activity. Further research into pharmacologic interventions for the treatment of the Insulin Resistance Syndrome appears very promising. We fully concur that the emergence of the Insulin Resistance Syndrome is among the most pressing problems of public health in the developed world, and many diverse talents and resources will need to work together to meet this challenge.
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