Reply to Letter to the Editor
Authors: B Walker
Journal: Cardiovascular Research (2002)

To the editor are not prolonged [3].Indeed, there is emerging evidence In our recent article [1], we observed close associations of the links between peripheral and hepatic insulin resistbetween higher blood pressure, higher fasting plasma ance (mediated for example by resistin, adiponectin, free glucose, and insulin resistance (as measured by fasting fatty acids etc) which makes it unlikely that these two are plasma insulin and the fasting insulin / glucose relationship ever truly dissociated in human disease.(HOMA)).Indices of microvascular structure in the skin So, while we certainly accept that differences in techwere associated with blood pressure and fasting plasma niques of measuring insulin sensitivity might attenuate glucose, but not with hyperinsulinaemia.We concluded relationships with microvascular structure, the question that altered microvascular structure may be an important remains of why we did not see any relationship at all while mediator of variations in blood pressure and fasting plasma Serne et al. have reported very strong correlations.One glucose, but is unlikely to explain their link with insulin issue is the characteristics of the participants.Our 105 resistance.participants did have a wide variation in blood pressure Erik Serne and colleagues contrast these findings with and insulin sensitivity (note the range of fasting insulin their own important body of work.They comment that our concentrations of 1.1-29.6mU / l, as stated in the manumeasurement of insulin resistance using fasting plasma script), but were homogeneous in other respects (all male, insulin reflects hepatic, rather than peripheral insulin age 23-33 y).Serne et al. studied a group of 18 men and sensitivity, and is less reproducible than the euglycaemic women with a wide age range (20-64 y).Although they hyperinsulinaemic clamp technique.It is implied that, had corrected for age and gender in their analysis, the validity we performed such clamps in our subjects, we would have of these corrections in such a small sample must be detected relationships between insulin resistance and mi-uncertain.Our study identified a further potential confouncrovascular structure.Clearly, we cannot exclude this der, since higher fasting plasma glucose was strongly possibility.However, given the lack of trends for correla-associated with fewer dermal capillaries and higher blood tions between fasting plasma insulin and microvascular pressure.Fasting glucose was not described in Serne et structure in our data, this would require remarkable al.'s previous paper, but it is known that higher fasting disparity between measurements of fasting hyperin-glucose levels at the beginning of a euglycaemic hysulinaemia and peripheral glucose disposal.Although the perinsulinaemic clamp will decrease apparent insulin senagreement between these techniques is, as Serne et al.sitivity measured by 'M value' [4].It would be important point out, not complete, it is over-simplistic to suggest that to know if this was a confounding variable in their they measure exclusively hepatic and peripheral insulin analysis.sensitivity, respectively.Apparently 'selective' peripheral Finally, these studies differ in the site and method of insulin resistance (e.g. in lipodystrophies and transgenic measurement of dermal microvascular structure; we animal models) is manifest by fasting hyperinsulinaemia counted all capillaries (whether continuously or intermit-[2]; while conversely, failure of suppression of hepatic tently perfused) on the dorsum of the middle phalanx, glucose production can affect 'M values' during hyperin-while Serne et al. measured continuously perfused capilsulinaemic euglycaemic clamps, particularly if the clamps laries immediately proximal to the nail fold.Both techniques measure differences which reliably predict blood pressure, but they do differ; in the nail fold fewer