Measuring Insulin Resistance and Secretion in Humans

Measuring Insulin Resistance and Secretion in Humans

Measuring Insulin Resistance and Secretion in Humans (#29)

Allan Vaag ¹

Rigshospitalet-Copenhagen University Hospital, Copenhagen, DK, Denmark

The assessment of in vivo pancreatic beta cell function as well as insulin action in humans is challenging because of a complex interplay between insulin secretion, insulin sensitivity and hepatic insulin extraction. Simplified, the relationship between insulin secretion and insulin sensitivity can be described by an approximate hyperbola with the product of the two variables being constant for individuals with the same degree of glucose tolerance (the disposition index). Strengths and limitations of the disposition index have been widely debated, and there is an increasing awareness of different measurements of both in vivo insulin secretion and of in vivo insulin action influencing the results and the interpretation of calculated insulin secretion disposition indices. Examples of differential results of insulin secretion disposition indices are the use of oral versus intravenous insulin secretion tests as well as the use of methods assessing in vivo insulin action preferentially measuring the degree of hepatic or peripheral insulin action. Examples of how uncritical use of common tests to measure insulin secretion and insulin action in humans may lead to erroneous results will be illustrated by recent studies of prediabetic subjects with impaired glucose tolerance (IGT) or impaired fasting glucose (IFG), from studies of subjects with genetic or non-genetic predisposition to type 2 diabetes, as well as results from human overfeeding and bed test studies. The underlying assumption in the use of the disposition index that the pancreatic insulin responds to insulin action is to some extent challenged by studies showing that increased insulin secretion may precede peripheral insulin resistance during short term overfeeding in humans. Finally the lecture will address another and until recently unrecognized dimension of the disposition index, namely the issue of adjusting insulin secretion for hepatic versus peripheral insulin sensitivity. An overall take home lesson from the lecture may be that none of the most commonly used in vivo tests of insulin secretion and of insulin action may be used uncritical as “gold standards”, but that the results from different tests should be interpreted within the physiological context in which the test was performed.

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Vaag, A

Chief Physician and Professor at Rigshospitalet and Copenhagen University, Denmark Prof Allan Vaag PhD, DMSc - Chief Physician and Professor at Rigshospitalet and Copenhagen University, Denmark Allan Vaag was born in 1961 and graduated as MD from the University of Southern Denmark in 1986. Since then, he has been engaged in various aspects of diabetes research with an emphasis on the pathophysiology of Type 2 diabetes (T2D). Allan Vaag holds clinical specialist recognition in Endocrinology and in General Internal Medicine. Allan Vaag wrote his ph.d.-thesis on the glucose-fatty acid cycle in humans including patients with T2D, based on a series of studies documenting for the first time that acute inhibition of lipolysis with a nicotinic acid derivative significantly improves insulin action in patients with T2D (Vaag et al, JCI, 1991). Based on eight original publications, Allan Vaag subsequently wrote his Master of Science Thesis on the current state of art of the pathophysiology of T2D (1999), including studies of prediabetic first degree relatives (Vaag et al, JCI, 1992, etc.) and monozygotic twins discordant for T2D (Vaag et al, JCI, 1995, etc.), Allan Vaag has for 10 years been heading a research group at the Steno Diabetes Center in Copenhagen focusing primarily on the impact of the prenatal environment versus genetics on the etiology and pathophysiology of T2D. In 2011, Allan Vaag was appointed full Professor of Endocrinology (Chair) at the Copenhagen University, situated at the Danish National State Hospital (Rigshospitalet), Copenhagen. The work of Allan Vaag is based upon detailed, extensive and well-powered integrative physiological studies of predominantly people at risk of T2D, which over the last two decades have documented a range of early genetic, epigenetic as well as non-genetic molecular defects of muscle and adipose tissue biology in T2D. For the last decade, one of his main interests has been in the role of the foetal environment in the development of T2D Allan Vaag was among the first to describe early defects of both insulin action, including impaired muscle glycogen synthesis, as well as defective insulin secretion in pre-diabetic subjects, contributing substantially to our present knowledge of T2D being not only a multi-factorial disease, but also a multiple organ disease involving muscle, beta cell, liver, adipose tissue, gut, and possibly also various other organ defects. Allan Vaag has authored more than 220 original papers and more than 50 review papers in the area of diabetes research in the leading international diabetes and medical journals including New England Journal of Medicine (NEJM), JCI, PNAS, Nature Genetics, PloS Medicine, Circulation, BMJ, Lancet, Diabetes, Diabetologia, Journal of Physiology, American Journal of Physiology, JCEM and many others. Allan Vaag´s current H-index is 45 and the total numbers of citations exceede 8000. Allan Vaag has since 2004 been adjunct professor of Metabolism and Clinical Diabetes Research at the Lund University, Sweden, and since 2011 he has been a faculty member and adjunct professor of endocrinology at the CMC Vellore, Tamil Nadu, India. Allan Vaag is Associate Editor of the European Journal of Endocrinology was until recently Senior Editor of the Journal of Physiology. He has serced in a number of national and international research councils including The Danish Strategic Research Council, Denmark, as well as the Swedish and the Finish research councils.

Measuring Insulin Resistance and Secretion in Humans (#29)

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