Metabolic Syndrome

At a Glance

A patient with type 2 diabetes and abdominal obesity may have other physical signs and abnormal laboratory findings that point toward an increased risk of coronary artery disease and increased morbidity/mortality. These may include dyslipidemia, hypertension, nonalcoholic fatty liver disease (including findings consistent with steatohepatitis) and hyperuricemia. All of these features are grouped into a category known as the metabolic syndrome.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

The metabolic syndrome is a constellation of findings that include insulin resistance and type 2 diabetes mellitus, as well as an abnormal lipid profile ("Dyslipidemia") that predisposes the individual to cardiovascular disease.

According to the consensus of the International Diabetes Federation (IDF) and the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI), the criteria for the metabolic syndrome includes 3 of the following:

  1. elevated waist circumference

  2. elevated triglycerides greater than or equal to 150 mg/dL

  3. reduced HDL-C, less than 40 mg/dL in males and less than 50 in females

  4. elevated blood pressure. Systolic greater than or equal to 130 mg/dL and diastolic greater than or equal to 85 mm Hg

  5. elevated fasting glucose greater than or equal to 100 mg/dL

Note that obesity and body mass index (BMI) and not an absolute prerequisite for the metabolic syndrome.

The Hemoglobin A1c can now be used in the diagnosis of type 2 diabetes. An A1c greater than or equal to 6.5% is diagnostic. The test should be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay. (Table 1)

Table 1

Test Results Indicative of the Disorder
Lipid Profile NCEP ATP III Guidelines hsCRP mg/dL
Triglycerides < 150 mg/dL
HDL-C > 40 mg/dL < 1 "Low"
LDL-C <100 mg/dL (optimal); 100-129 mg/dL (near optimal) 1-3 "Medium"
> 3 "High"
Non-HDL-C <130 mg/dL

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

Lipid lowering-drugs, such as statins may very rarely cause hepatotoxicity and thereby elevate liver enzymes. Myopathy is a more likely adverse effect of statins, but even this is very uncommon. If myopathy were to occur, an elevation in creatine kinase (CK) and AST would be expected to occur.

hs-CRP may be elevated as a result of any source of inflammation. Therefore, a patient in the hospital, especially with a known infection, post-operative or post-trauma would not be a candidate for this analysis.

What Lab Results Are Absolutely Confirmatory?

There is no single laboratory test that is confirmatory for the metabolic syndrome. Indeed, the controversy over this syndrome is largely related to how closely one believes all the associated features are related.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Non-Alcoholic Fatty Liver Disease (NAFLD)

Fatty liver is common in obesity and the metabolic syndrome. NAFLD has a prevalence in western societies of approximately 25-30%. The prevalence of NAFLD is 55-70% in obese individuals and approximately 50% of people with diabetes mellitus. NAFLD is a common cause of abnormal liver function tests among adults in the United States.

This condition is best diagnosed by imaging techniques, but clinicians and laboratorians should be aware that it may produce abnormal results, such as elevated liver enzymes (as in this case), particularly during episodes of inflammation or steatohepatitis. A liver biopsy, if performed, may show macro- and microvesicular steatosis, Mallory hyaline, and features of cholestasis.

Apolipoprotein B determination

LDL particle number, rather than LDL cholesterol, is a better predictor of cardiovascular risk. One method of assessing particle number is to determine Apo B concentration. The other advantage is that Apo B is present on other potentially atherogenic particles, such as VLDL and IDL and Lp(a).


High ferritin concentrations may be present in individuals with the metabolic syndrome. There is an enigmatic link between ferritin, insulin resistance, and NAFLD.

Total Testosterone

Concentrations are frequently decreased (<300 ng/dL) in adult males with metabolic syndrome. Like ferritin, the exact role of this phenomenon is unclear, that is, whether the low testosterone or the metabolic syndrome comes first.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

Fatty liver and steatohepatitis may be a consequence of alcohol abuse.

Elevations in ferritin concentration may be seen in chronic iron overload, acute inflammation, and hepatitis.

Low serum testosterone concentrations in males may be due to hypothalamic/pituitary disorders (low FSH and LH) or be primary gonodal (high FSH or LH or both).

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