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Figure 1.1 Number of original papers (dark columns) and reviews (light columns) in five-year intervals from 1970 to 2005 based on MEDLINE searching for the terms 'diabetes' or 'metabolic diseases'.

Despite the rising interest in clinical research, many basic questions regarding metabolism in humans are unanswered or have not been addressed in sufficient detail. A major issue is the role of aging in intermediary metabolism. which was studied in detail in vivo in humans only recently. Petersen et al. (2004) assessed glucose fluxes and ectopic lipid deposition as well as mitochondrial oxidation and phosphorylation under in vivo conditions and found ~40 % lower flux rates through the tricarboxylic acid cycle and adenosine-tris-phosphate synthesis, possibly explaining the reduced insulin sensitivity and elevated ectopic lipid content in elderly humans. Nevertheless, it remains unclear whether aging is generally associated with impaired insulin sensitivity; specific genetic or even acquired abnormalities could be responsible for reduced mitochondrial function not only during aging but also in other metabolic disorders (Stark & Roden 2007). Likewise, sex and ethnicity can variably affect metabolic characteristics including body fat and its distribution, lipid metabolism and insulin action, which further complicates interpretation of clinical metabolic studies (Woods et al. 2003; Carulli et al. 2005).

These aspects of human metabolism culminate in the recent discussions on definitions of metabolic disorders summarised by the term '(dys)metabolic syndrome' or 'syndrome X', which was introduced by Reaven about 20 years ago (Reaven 1988) and increasingly studied over the next decades (Figure 1.2). The World Health Organisation (WHO), the European Group for Insulin Resistance (EGIR), the Adult Treatment Panel (ATP III) and the International Diabetes Foundation (IDF) re-defined the metabolic syndrome, and more definitions are coming up due to different combinations and cut-off points of continuous variables, such as fasting plasma glucose, triglycerides or variable indices of body fat content (Table 1.1). The current discussion focuses on the relative importance of the compounds of the metabolic syndrome and the issue of whether it is a syndrome at all (Kahn et al. 2005). This controversy mostly results from different interpretations and understandings of this term, which can be used 1) to explain a series of factors by one underlying causal factor, be it insulin

Number of publications

Number of publications

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