Metabolic Syndrome: Clinical Issues

Endocrine Society Symposium
Thursday June 17, 2004
3:45 – 5:45 PM

Reviewed by Joelle Escoffery, PhD

This symposium addressed the epidemiology of and treatment options for the metabolic syndrome.  According to the National Cholesterol Education Program (NCEP), the metabolic syndrome is comprised of any 3 of the following: increased waist circumference, high fasting triglycerides, low HDL, high blood pressure, and high fasting glucose.  Other factors that are not part of the definition of metabolic syndrome but may also be important include abnormal lipid composition (eg, small dense HDL and LDL particles) increases in apolipoprotein B, uric acid, fibrinogen, PAI-1, dimethylargenine, circulating cytokines, and decreases in adiponectin, all of which are associated with increased cardiovascular risk. Presence of the metabolic syndrome has been associated with increases in cardiovascular disease mortality, cerebrovascular disease, and all cause mortality. When the relationship between the metabolic syndrome, diabetes, and CHD was examined, there was a 50% increase in CHD prevalence among people with metabolic syndrome but no diabetes.  Among people with metabolic syndrome and diabetes, there was a 2.5 fold-increase in CHD prevalence. However, among people with diabetes who did not have symptoms of the metabolic syndrome, there was no increased risk of CHD.  Thus, the elevated risk of CHD seen in diabetes may be related to the presence of metabolic syndrome.

Treatment for the metabolic syndrome should have two main goals: reducing risk for type 2 diabetes and reducing risk for cardiovascular disease.  Three different approaches to achieving these goals include weight loss, treatment of insulin resistance, and treatment of cardiovascular risk. Although weight loss has been shown to be an effective strategy to reduce diabetes risk and cardiovascular risk, weight management interventions have not been effectively integrated into real-world clinical settings.  Pharmacologic treatment of metabolic syndrome has begun to be investigated. Specifically, agents that target insulin resistance, such as metformin, thiazolidinediones (TZDs), and acarbose may have benefits. An alternate approach would be to address cardiovascular risk through the use of statins, fibrates, ACE inhibitors, ARBs, aspirin, and others.  Although pharmacologic agents are available, weight loss was recommended as the first line of treatment.

Another approach to the management of metabolic syndrome is to focus on fitness as opposed to weight loss.  Fitness is generally operationalized as low fit (bottom 20%), moderately fit (middle 40%), and high fit (top 40%). A series of compelling studies demonstrated great benefits associated with moving from the low fit group to the moderate fit group, which can be achieved with 150 minutes a week of physical activity.  A direct relationship between fitness and cardiovascular mortality was shown in healthy people, people with hypertension, and people with diabetes. Interestingly, this relationship holds, even after controlling for weight.  Stated differently, it is more beneficial to be overweight and fit than to be lean and unfit. Although there are no randomized controlled trials examining fitness and metabolic syndrome, re-examination of data collected for a different purpose showed that a 20-week exercise intervention was associated with decreases in triglycerides, blood pressure, hyperglycemia, and prevalence of metabolic syndrome.  Future trials are being designed to examine this issue prospectively.