What is the value of assessing insulin resistance?

A:Insulin resistance (IR) is an independent risk factor for the development of metabolic syndrome and type 2 diabetes. In recent years, there has been widespread scientific interest in this topic, as it has become apparent that IR develops early in the pathological process leading to diabetes. Many studies have shown that it may predate the onset of diabetes by 10–20 years.

What are the causes of IR?

Many roads lead to IR, but genetics and the environment are strong predisposing factors. Congenital factors like fetal undernutrition and ethnic differences can lead to IR, as can molecular defects such as genetic mutations that cause insulin receptor defects or post-binding signaling. Acquired factors also trigger IR, including those that are physiological (pregnancy, puberty, high-fat diet, physical inactivity, aging); hormonal (corticosteroids, acromegaly, pheochromocytoma, polycystic ovary syndrome); or that fall outside of these categories (hypertension, liver cirrhosis, sepsis, surgery, burns and trauma, auto-antibodies to insulin receptor).

How is IR being used in research and clinical practice?

The quantitative assessment of IR has many applications in the context of research. This includes epidemiological studies, physiological examinations, therapeutic interventions, and other research areas. IR has yet to make its mark in clinical practice. Although IR can be inferred from clinical findings, it is not currently common practice to quantitate it in routine clinical settings or applications.

What methods are available to assess IR?

One reference technique for assessing IR is the hyperinsulinemic euglycemic clamp (HEC). An alternative technique is the frequently sampled intravenous glucose tolerance test (FSIVGTT), while the oldest method is the insulin tolerance test. In these interventional dynamic techniques, blood samples are collected serially. They cannot be applied in routine clinical investigation, however, as they are difficult, time-consuming, and potentially hazardous for the patient due to the consequence of hypoglycemia.

Simple, non-invasive indices have also been proposed, owing to their ease of application and convenience to patients. Simple indices derived from fasting levels of glucose and insulin—especially the homeostasis model assessment and the quantitative insulin sensitivity check index—are the most commonly used tools for estimating IR. Some others can be derived from oral glucose tolerance testing using fasting and non-fasting blood samples. Additionally, biochemical markers such as fasting insulin, sex hormone binding globulin, and insulin-like growth factor binding protein 1 levels can provide useful information about IR status.

How do we select the most suitable method for assessing IR?

Given the increasing number of indices of IR, it may be difficult to select the most appropriate index. Despite their accuracy, the HEC and FSIVGTT reference techniques are dedicated for research purposes only. Labs should consider these general factors before using either: prior knowledge of the method and its limitations; setup and facilities; budget; number of investigated subjects; and ability to share information with experts on these methods.

Owing to their easy use and convenience when investigating a large number of subjects, simple indices are the most commonly used tools for both clinicians and researchers. There are many simple indices, but labs should consider the following criteria before choosing one: number of samples to be collected from each individual; endogenous insulin status; clinical condition; insulin assay criteria; other analytes to be tested (e.g. C-peptide, fatty acids); the formula utilized; and biological variation.

What are the obstacles to assessing IR in clinical laboratory applications?

Before using simple indices of IR in routine clinical laboratory investigations, certain obstacles need to be overcome. These include insulin assay standardization and the absence of reliable reference intervals or clear cut-off values. Once these factors have been established, the indices of IR can be provided as part of routine clinical laboratory tests.

Anwar Borai, PhD, MLS(ASCP), is a clinical scientist in clinical chemistry at King Abdulaziz Medical City, assistant professor at King Saud bin Abdulaziz University-Health Sciences, and a research scientist at King Abdullah International Medical Research Center in Riyadh, Saudi Arabia. +Email: boraiaa@ngha.med.sa