Rlo Homeostasis

yes

optional

+

1. See Chapter 3 for a discussion of the indices.

2. Tests requiring C-peptide also require software for deconvolution. C-peptide deconvolution can be used with all tests.

3. Complexity ranking is somewhat subjective (+ = simplest; + + + + + = most complex).

4. The infusion pump is used for insulin infusion in insulin-modified IVGTT.

5. Modeling software to calculate additional (3-cell function indices is optional.

6. The IVGTT complexity depends remarkably on the specific protocol used and on the data analysis procedures.

1. See Chapter 3 for a discussion of the indices.

2. Tests requiring C-peptide also require software for deconvolution. C-peptide deconvolution can be used with all tests.

3. Complexity ranking is somewhat subjective (+ = simplest; + + + + + = most complex).

4. The infusion pump is used for insulin infusion in insulin-modified IVGTT.

5. Modeling software to calculate additional (3-cell function indices is optional.

6. The IVGTT complexity depends remarkably on the specific protocol used and on the data analysis procedures.

COMPARATIVE EVALUATION OF METHODS Table 2.2 Practical Considerations

• Select test considering:

o Desired (-cell function indices; o Test complexity;

o Availability of laboratory equipment and software for data analysis; o Possibility of also assessing insulin sensitivity.

• Use intravenous standardised tests if appropriate normalisation to glucose levels is difficult.

• Keep in mind that very simplified tests have limited reliability.

• Verify on the original references the protocol details, dosages and sampling schedule before planning experiments. Strict observance of the protocol is important for test quality.

• Use reliable insulin (and C-peptide) assays and perform measurements accurately.

• Use C-peptide to calculate insulin secretion by deconvolution when possible.

• If the test is used to compare groups, be sure that tests yield results that are comparable. For instance, hyperglycaemic clamps at different glucose levels are not comparable.

• Keep in mind that (-cell function may depend on insulin resistance. For instance, first phase secretion indices from the IVGTT cannot be compared if insulin sensitivity is different.

• Use caution with indices that express (-cell function in relation to insulin sensitivity (in particular with the disposition index). The assumptions under which these indices are valid must be verified.

experimentally very cumbersome. On the other hand, the IVGTT is only partially standardised: assessment of second phase secretion requires empirical or modeling procedures analogous to those of the oral tests.

Oral tests have the difficulty of requiring appropriate methods for normalisation of the secretory response to the stimulus. Empirical parameters, such as the insulinogenic index, do not have a clear physiological interpretation and sometimes exhibit outliers (very high or negative values). Modeling methods have the advantage of providing p-cell parameters with a better physiological basis and have proved to be quite effective for assessing the role of p-cell function in various pathophysiological states (e.g. Camastra et al. 2005; Ferrannini et al. 2005). In addition, with oral tests, in contrast to intravenous tests, p-cell function is evaluated in conditions that are closer to those of normal living. This has been of remarkable usefulness in the evaluation of drug efficacy (Mari et al. 2005b, 2005c). Thus, oral tests with modeling analysis are an interesting option to consider, although the practical difficulties of the modeling analysis may be an obstacle.

Oversimplified tests such as HOMA-B have a rather limited power and reliability. They should not be regarded as real option for p-cell function assessment when a study is designed, but rather as a last resort for the interpretation of already collected data. In this way, if the necessary caution is used in interpretation, such approaches may have some value.

A difficulty in the comparative evaluation of p-cell function tests is that our current understanding of the p cell is insufficient to envisage a single p-cell parameter (or a small number of indices) fully representative of the p-cell status. Although different p-cell function indices may be correlated, this is not necessarily always the case (Ferrannini & Mari 2004). Progress towards a better and simpler characterisation of p-cell function may be expected from our constant advancements in the understanding of the p cell. At present, however, assessment of P-cell function requires multiple indices, and thus is, in practice, inevitably incomplete and often approximate.

Conclusion

This review has shown that many methods for the assessment of P-cell function are available. The existence of several approaches is to a substantial extent dictated by the fact that the P-cell response is complex, and no single test is sufficient for a complete characterisation of P-cell function. Since every method has its inevitable limitations, the choice should be guided by a critical examination of test characteristics in relation to the investigator's needs and constraints. In addition, whatever approach is used, when the results are interpreted the nature and limitations of the test should be kept in mind in order to avoid overinterpretation. We hope that the present discussion has been helpful in achieving these goals.

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