NDT Advance Access originally published online on August 8, 2007
Nephrology Dialysis Transplantation 2007 22(11):3359; doi:10.1093/ndt/gfm526
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Correspondence and offprint requests to: Email: joran{at}online.noSir,
We appreciate the interest shown in our article by Soypacaci and Keven, and agree that the hyperinsulinemic euglycaemic clamp is considered to be the gold standard for measuring insulin sensitivity (IS) [1]. However, since the diabetogenic effect of ciclosporin A (CsA) is considered to be caused by impaired insulin synthesis or secretion, the main objective for our study was to investigate any detrimental effect of CsA on insulin secretion [2]. The hyperglycaemic clamp method is considered the gold standard for assessing insulin secretion [1–3]. Second, glucose clamp studies are cumbersome, expensive and time consuming procedures, both for patients and investigators. To avoid an additional time consuming procedure such as a hyperinsulinemic euglycaemic clamp, we decided to use the 3 h hyperglycaemic clamp method which also allows a reliable estimate of IS during the 3rd hour of the clamp to be calculated (glucose disposal rate divided by mean insulin level = IS index; ISI) [2,3]. Although the ISI values obtained with hyperglycaemic clamp are usually higher than those obtained with euglycaemic clamp, they are highly correlated (r = 0.84, P < 0.0001) [3]. Further, no patient had diabetes, and the average levels of serum insulin during the last hour of the clamp (3–500 pmol/l) are comparable with the insulin levels measured during euglycaemic clamp studies. These insulin levels are most probably sufficient to suppress hepatic glucose production and output. In view of this, and since the mean change in IS was the main secondary outcome of the study, we argue that our estimates of IS are appropriate and comparable with those derived from euglycaemic clamp studies. Importantly, the power to reveal any small change in IS was obviously limited by the relatively low number of patients included in the study.
1Morbid Obesity Center
Vestfold Hospital Trust, Boks 2168
3103 Tønsberg, Norway
2Section of Nephrology
Department of Medicine
Rikshospitalet University Hospital
University of Oslo
0027 Oslo, Norway
3Department of Pharmaceutical
Biosciences, School of Pharmacy
University of Oslo, Norway
4Institute of Clinical Medicine
University of Tromsø, Norway
References
- DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol (1979) 237:E214–E223.[Web of Science][Medline]
- Hjelmesæth J, Hagen LT, Asberg A. The impact of short-term ciclosporin A treatment on insulin secretion and insulin sensivity in man. Nephrol Dial Transplant (2007) 22:1743–1749.
[Abstract/Free Full Text] - Mitrakou A, Vuorinen-Markkola H, Raptis G, et al. Simultaneous assessment of insulin secretion and insulin sensitivity using a hyperglycemia clamp. J Clin Endocrinol Metab (1992) 75:379–382.[Abstract]
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