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      Drugs & Diseases > Endocrinology

      Insulin Resistance Workup

      Updated: Jul 08, 2020
      • Author: Samuel T Olatunbosun, MD, FACP, FACE; Chief Editor: George T Griffing, MD  more...
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      Workup

      Approach Considerations

      In clinical practice, no single laboratory test is used to diagnose insulin resistance syndrome. Diagnosis is based on clinical findings corroborated with laboratory tests. Individual patients are screened based on the presence of comorbid conditions.

      Next:

      Lab Studies

      Routine laboratory measurements in the evaluation of patients with insulin resistance syndrome include the following:

      • Plasma glucose level (fasting, random, and oral glucose tolerance test) - Diagnosis and monitoring of glucose intolerance (diabetes mellitus, impaired glucose tolerance [IGT], impaired fasting glucose [IFG]).

      • Insulin resistance - May also be associated with hypoglycemia (autoimmune conditions).

      • Glycohemoglobin level – Used to assess chronic hyperglycemia.

      • Fasting insulin level - A measure of the degree of insulin resistance in many patients with insulin resistance syndrome.

      • Lipid profile (fasting total cholesterol, low-density lipoprotein [LDL], high-density lipoprotein [HDL], cholesterol, triglyceride) - Insulin resistance syndrome characterized by elevated LDL-B levels (small, dense, pattern B), high triglyceride levels, and reduced HDL-C levels.

      • Combined use of insulin and lipid markers in atherosclerosis - Fasting insulin, apolipoprotein B, and small LDL levels are more biologically significant than are standard lipid tests. Elevations in the 3 markers increase the risk of coronary artery disease by nearly 20-fold.

      • Electrolyte levels (BUN [blood urea nitrogen], creatinine, and uric acid levels) - Hyperuricemia is common and is often considered a component of the metabolic syndrome.

      • Urinalysis - Microalbuminuria is a marker of endothelial dysfunction.

      • Homocysteine (H[e]) - An elevated level is a risk factor for atherosclerosis, which predicts macrovascular disease. levels are regulated by insulin.

      • Plasminogen activator inhibitor (PAI)-1 - An elevated level is associated with insulin resistance syndrome and is correlated with obesity, waist-to-hip ratio, hypertension, fasting and postprandial insulin levels, proinsulin levels, fasting glucose levels, and elevated triglyceride and LDL levels. [53] An increased PAI-1 level signifies impaired fibrinolysis, thus indicating increased risk of atherosclerosis.

      Other laboratory studies include measurement of fibrinogen levels and testing of endothelial function. An increased fibrinogen level is a feature of insulin resistance syndrome. Endothelium plays an important role in insulin action, including in the regulation of tissue blood flow and in insulin delivery to interstitium. Endothelial dysfunction is an important component of insulin resistance syndrome and includes reduced capillary formation, reduced surface area, and abnormal reactivity of endothelium. [54]

      Most recently, serum WISP-1/CCN4 level (WNT1 inducible signaling pathway protein 1), a novel pro-inflammatory adipokine, was proposed as a suitable biomarker of obesity, and the levels correlate with anthropometric indices of obesity. [55]

      Biochemical changes associated with endothelial dysfunction include (1) reduced nitric oxide and prostacyclin levels, (2) increased endothelin and angiotensin activity, and (3) increased local and systemic inflammation (increased C-reactive protein [CRP] levels). [4] Blood testing for CRP measurement is widely available. Smoking and abnormal lipids are major contributors to endothelial dysfunction.

      In theory, insulin sensitivity can be assessed through the following methods:

      • Fasting insulin level - This provides an indirect assessment of insulin sensitivity. The limitation of this study is inaccuracy in a patient with mutant insulin in which the hormone measured by radioimmunoassay is not fully bioactive.

      • Measurement of response to direct intravenous infusion of insulin - The limitations of this measurement are a confounding factor in data interpretation and a variation in secretion of antagonist hormones in response to hypoglycemia.

      • Euglycemic insulin clamp technique - Plasma glucose levels are held constant, with variable glucose infusion. Biochemical responses that are surrogate estimates of insulin resistance, such as glucose disposal and antilipolysis, are determined. This method is considered the criterion standard.

      • The latter two tests are more accurate, but they are research tools and are not routinely used in clinical practice.

      • Homeostatic model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) - These are the most widely used simple indices for assessing insulin resistance in clinical research and practice. Both indices are based on fasting glucose and insulin measurements; they differ mainly in the log transformation of these variables in QUICKI. [56, 57, 58]

      • HOMA-IR is derived from the product of the insulin and glucose values divided by a constant--that is, calculated by using the following formula: fasting glucose (mg/dL) X fasting insulin (µU/mL) / 405 (for SI units: fasting glucose (mmol/L) X fasting insulin (µU/L) / 22.5). A value greater than 2 indicates insulin resistance.

      • QUICKI is derived by calculating the inverse of the sum of the logarithmically expressed values of fasting insulin and glucose: 1/[log(fasting glucose) + log(fasting insulin)] . It measures insulin sensitivity, which is the inverse of insulin resistance. A value of less than 0.339 indicates insulin resistance.

      • They both compensate for fasting hyperglycemia, and the results for the indices correlate reasonably well with the euglycemic clamp technique. Some investigators believe that QUICKI is superior to HOMA-IR (for instance, in reproducibility), but the two indices correlate very well. [59, 60, 61]

      • One study suggests fasting insulin sensitivities are not better than routine clinical variables in predicting insulin sensitivity in black Africans. [62]

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      Other Tests

      Other cardiac tests include echocardiography and stress testing, depending on the presentation.

      A risk-assessment calculator, based on data from the Framingham Heart Study for estimating 10-year cardiovascular risk, is available. This calculator estimates the 10-year risk for hard coronary heart disease outcomes (myocardial infarction and coronary death). The tool is designed to estimate risk in adults aged 20 years and older who do not have heart disease or diabetes. The ACC/AHA Pooled Cohort Equations CV Risk Calculator was developed as a 10-year risk assessment tool for atherosclerotic cardiovascular disease from multiple community-based cohorts (including the Framingham Heart study). [63]

      For patients with insulin resistance without overt diabetes, the metabolic syndrome criteria for cardiovascular risk stratification are less sensitive than those of the Framingham Risk Score, which takes into account age, total cholesterol, tobacco use, HDL-C, and blood pressure, but not diabetes.

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