Measurement Of Insulin Resistance And Clinical Assessment

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Clinically, a number of techniques have been developed to detect the presence of insulin resistance and assessments vary in complexity and precision (Figure 2.2)2-6. However, from a clinical perspective, the most practical way of assessing insulin resistance is the measurement of plasma insulin levels. (Insulin is produced in pancreatic p-cells and is released into the bloodstream in response to stimulation that occurs after a meal ingestion (Figures 2.3 and 2.4)7. As type 2 diabetes is characterized by an antecedent phase of insulin resistance that requires a compensatory increase in insulin secretion to maintain euglycemia, an elevated insulin level in the fasting state is indicative of insulin resistance.) It is suggested that this be performed in the overnight fasting condition, since in the postprandial state glucose levels are changing rapidly, and variable levels of glucose confound the simultaneous measurement of insulin. The homeostasis model assessment (HOMA)4,5 of insulin sensitivity is a simple, inexpensive alternative to more sophisticated techniques and derives an estimate of insulin sensitivity from the mathematical modeling of fasting plasma glucose and insulin concentrations. Specifically, an estimate of insulin resistance by HOMA score is calculated with the formula: (fasting serum insulin (^.U/ml) x fasting plasma glucose (mM))/22.5. Oral glucose tolerance testing (OGTT) enables the insulin secretory response to an oral glucose challenge to be calculated6. The frequently sampled intravenous glucose tolerance test (FSIVGTT) is a method that is less invasive and more practical than the euglycemic hyperinsulinemic clamp technique and one that can be applied to larger populations2,3. With this procedure, glucose is injected as a bolus, and both glucose and insulin levels are assessed frequently from an

Inflammatory markers

Diabetes (type 2)

Raised blood pressure

Inflammatory markers

Cardiovascular disease

Figure 2.1 Illustration of traditional and non-traditional factors associated with cardiometabolic risk indwelling catheter over the next several hours. The results are entered in a computer model that generates a value as an index of insulin sensitivity, termed SI units.

The most widely accepted research gold standard is the euglycemic hyperinsulinemic clamp technique2,3. In this procedure, exogenous insulin is infused to maintain a constant plasma insulin level above fasting, whereas glucose is infused at varying rates to keep glucose within a fixed range. The amount of glucose that is infused over time (M value) is an index of insulin action on glucose metabolism. As described, the more glucose that has to be infused per unit time to maintain the fixed blood glucose level, the more sensitive the patient is to insulin. With this procedure, the insulin-resistant patient requires much less infused glucose to maintain the basal level of glucose. Studies that have used any or all of these techniques have

Figure 2.2 Techniques used to assess insulin resistance. HOMA, homeostasis model assessment; OGTT, oral glucose tolerance test; FSIVGTT, frequently sampled intravenous glucose tolerance test; EH clamp, euglycemic hyperinsulin-emic clamp

demonstrated that there is a wide range of insulin sensitivity in normal individuals, and that these levels may overlap with values obtained in subjects with type 2

Table 2.1 Human diseases and conditions characterized by insulin resistance. From reference 1, with permission

Insulin resistance may be

Insulin resistance associated with

Insulin resistance may be primary


genetic syndromes

Type 2 diabetes mellitus


Progeroid syndromes (e.g. Werner's syndrome)

Insulin resistance syndrome

Type 1 diabetes mellitus

Cytogenetic disorders (Down's, Turner's, and

(syndrome X)

Type B severe insulin resistance


Gestational diabetes mellitus


Ataxia telangiectasia

Type A severe insulin resistance


Muscular dystrophies

Lipoatrophic diabetes

Acute illness and stress

Friedreich's ataxia


Cushing's disease and syndrome

Alstrom syndrome

Rabson-Mendenhall syndrome


Laurence-Moon-Biedl syndrome



Pseudo-Refsum's syndrome

Atherosclerotic cardiovascular


Other rare hereditary neuromuscular disorders


Liver cirrhosis

Renal failure

diabetes. Furthermore, even at similar levels of body mass index (BMI), there appear to be ethnic differences in the degree of insulin sensitivity (Figure 2.5)8. Therefore, it is very difficult to distinguish between non-diabetic and diabetic individuals on the basis of insulin resistance.

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